Effects of electrical polarization on inner hair cell receptor

potentials
Peter Dallos and Mary Ann Cheatham
AuditoryPhysiology
Laboratory(HughKnowlesCenter)andDepartmentofNeurobiology
andPhysiology,
NorthwesternUniversity,
Evanston,Illinois60208

(Received18August 1989;acceptedfor publication20 December1989)

Ac and dc receptorpotentialcomponents
in responseto tone-burststimuliweremeasured
from innerhair cellsin the third cochlearturn of the guineapig. Comparisons
weresought
betweenconditionswhenconstantpolarizingcurrentwasinjectedinto the cell throughthe
recordingelectrodeand whentherewasno extrinsiccurrent.Hyperpolarizationof the cell
increased
all responses,
whiledepolarization
decreased
them.The input-outputfunctionswere
verticallytranslatedby currentinjection.The extentof translationwasa functionof current
level. In addition,the amountof current-inducedchangewasfrequencydependent.Largest
changeswereseenat low frequencies
and the current-induced
changetendedtowarda constant
high-frequency
asymptotebetween1-2 kHz. Changesin the dc response
componentwere
considerablyin excessof thosefor the fundamentalac response.The frequency-dependent
effectsare quantifiedwith the aid of a hair cell circuitmodel [ P. Dallos,Hear. Res. 14, 281291 (1984) ]. It is assumedthat the quantityalteredby polarizingcurrent(actuallyby the
transmembrane
voltage)is the resistance
of the cell'sbasolateralmembrane.
PACS numbers: 43.64.Ld, 43.64.Bt, 43.64.Kc

INTRODUCTION

Electricalpolarizationhasbeenusedfor decadesin order to alter cochlearresponses

(e.g.,TasakiandFerntndez,
1952;Konishi and Yasuno, 1963;Dallos et al., 1969;Mountain, 1980; Nuttall, 1985). Currentsdeliveredinto the fluid
compartmentsof the cochleacan haveprofoundeffectson
electricalresponses,
both pre- and post-synaptic(e.g., Tasaki and Fern/tndez, 1952), on cochlear distortion (e.g.,
Dallos et al., 1969), andon cochlearmechanics(e.g., Mountain, 1980). Currentsdeliveredinto the receptorcellsthemselvesalter their operatingpointandmay changetheir electrical responsiveness
(e.g., CrawfordandFettiplace,1981).
The current-voltagerelationshiphasalsobeenexaminedin
differenthair cell types (e.g., Hudspeth and Corey, 1977;
Russell, 1983;Russellet al., 1986). Possibleinfluenceof intracellularpolarizationupona cell'sfrequencyresponse,as
measuredby both its ac and dc receptorpotentials,hasnot
beenstudied.It is the purposeof this paperto providesome

A windowwasopenedin theboneoverthe striavascularis;the cochleawasbacklightedto aid in aimingthe electrode toward the shadowof the organ of Corti. The electrodeswere introducedthrough the stria, through scala
media,and into the organof Corti, trackingparallelto the
reticularlamina.The recording(and current-passing)
electrodes were fabricated from 1.2-mm-o.d. glass with a
Brown-Flaminghorizontal puller. They were backfilled
with 2M KAc and had resistances
rangingbetween80 and
150Mfg. Preamplificationandcurrentpassingwereaccomplishedwith a high-impedance,capacitance-compensated
amplifier/constantcurrent sourcebridge circuit (Dagan
8700).

Dc currentwascontinuouslyinjectedduringdata collectionperiodswhen sucha manipulationwas called for.

The current was derived from the constant-current

circuit of

the Dagan8700.It is well known(e.g.,Lava16eet al., 1969)

that high-impedance
electrodes
changetheir characteristics
when
current
is
passed
through
them. Most rectify and
information on this matter.
changetheir tip impedance.With an increasein electrode
resistance,the cutofffrequencyof the low-passfilter formed
I. MATERIALS
AND METHODS
by the tip resistance
and straycapacitance
is lowered.The
usualcutofffrequencyof thisfilteris roughly1500Hz after
We haveusedour conventionallateralapproachto hair
capacitance
compensation.
Thiscanbemeasured
by passing
cellsin the guineapig'sorganof Corti (Dallos et al., 1982).
small ac currentsthrough the recordingelectrodeand reDetailed information on surgery,animal maintenance,and
cording the resulting voltage drop. Any current-related
instrumentationhasappearedbefore(Dallos, 1985a). Conchangewould affectthe high-frequency
response,without
sequently,
onlya fewsalient
issues
arerepeated
here.
significantlymodifyinglow frequencies.As shownbelow,
Young albinoguineapigswere anesthetizedand mainour resultsindicateprimarily low-frequencychangesin the
tainedwith urethane.The right auditorybulla wasexteriorIHC response
dueto dc currentinjection.Consequently,
the
ized and opened.A closed,calibratedsoundsystemwascoufor them.It is possipled to the bony external meatus. All data for these electrodeartifactcannotbe responsible
ble, indeedlikely, that changingelectrodefiltering due to
experimentswere recordedfrom inner hair cells (IHC) in
Sucheffects
the third cochlearturn. Thesecells have best frequencies currentdoesaffecthigh-frequencyresponses.
between 800 and 1000 Hz.
would be particularly noticeablefor harmonicresponses,
1636

J. Acoust.Soc. Am. 87 (4), April 1990

0001-4966/90/041636-12500.80

@ 1990 AcousticalSocietyof America

1636

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whosefrequencies
arerelativelyhighevenfor lowerfrequency fundamentals.The presentpaperdoesnot dealwith these

harmonics.

Several measurements

were taken with electrodes hav-

ing typical resistancevalues,and usingthe usual rangeof

polarizingcurrents,with the tip dwellingin scalamedia,in
the organof Corti fluid spaceor within a supportingcell.
Measurementsof stimulus-evoked
ac and dc responses
at
theselocationsrevealedminimal changesbelow the electrode'scutofffrequencydue to the currentinjectedthrough
the electrode.Thus one may concludethat the current-dependenteffectsthat are describedbeloware not attributable
to changesin electroderesistance.Specifically,neither the
frequency-dependent
changesin the ac response,nor the
large alterationsin the dc responsedue to current can be
attributedto the recordingelectrode.
Stimuli were generatedby a computer-controlledfrequencysynthesizer(Rockland) anda customgatingdevice.
Signalsequences
weremenu-controlled,
typicallyconsisting
of eithera frequencyseriesmeasuredat constantsoundlevel
or a levelseriesmeasuredat constantfrequency.Amplified
receptorpotentialswereaveragedon-line(PDP-11/73) and
the completedaveragewas stored in memory. Raw data
were also storedon a 16-bit PCM-equippedvideo tape recorder.Prior to eachexperimentalrun, the gain of the system wasautomaticallyoptimizedsothat the signalinto the
A/D input would be as big as possiblewithout driving the
systeminto saturation.Anti-aliasfilteringwasintroducedat
3000 Hz. Harmonic magnitudeand phaseinformationwas
obtainedoff-linefrom windowed,averagedresponses
with
fastFourier transformation.The dc componentof the receptor potentialwasmeasuredfrom averagedwaveformsasthe
differencebetweenone-halfof the peak-to-peakac response
and the baselinein quiet. This measure,of course,doesnot
givea true meanvaluesincethe waveformisdistorted.However,we find that, with noisybiologicaldata, this measureis
more reliable than the true mean obtained

from

Fourier

analysisof relatively short-durationresponses.

Illustrative
responsewaveformsfrom two inner hair cellsin the same
organof Corti are presentedin Fig. 1.
II. RESULTS

-2 nA

110 210 31 0 41 0 51 0 61'0

,

UI,,

0nA

'

'

'

0 nA

+1
nAUL

UI'

+1
nA

11 0

Time
(mS)Goin:200.OX

21 0

31 0

41 0

51 0

61 0

tie(ms)Goin:200.OX

FIG. 1. Averagedresponse,waveforms
(labeled"raw data") obtainedfrom
two inner hair cells in the samecochlea. In both, the stimulus is 700 Hz at 70

dB SPL. The threetraces,from top to bottom,depictresponses

with -- 2-,
0-, and + 1-nA current levels. Left traces are obtained in an IHC encoun-

teredduring the third electrodepassthrough the organ,thosein the right

column,duringthe fourth pass.Responses
measuredin the organof Corti
fluid space,bracketing in time the data collection from IHCs, were unchanged.The majority of data reportedhere are from the cell in electrode
track #4. Verticalscalefor all panels:+_16 mV.

mV. This decreasedto approximately --24 mV within 2

min after penetrationand then remainedsteady.Contact

withthecellwasmaintained
for 53 min.'Organof Corti
responses
weremeasured
beforepenetrationandafterlossof
the IHC, and they remainedinvariant.This signifiesthe stability of thepreparationoverthe recordingperiodof interest.
In Fig. 2, ac magnitudefunctionsare shownfor a frequency(700 Hz) that is somewhatbelowthe BF for two
polarizingcurrentlevels, + 1 and -- 2 nA, and for the nocurrentcondition.The functionsappearto shiftin the vertical directionwithoutchangingshape.With hyperpolarizing
(negative)current,thereisan increasein response;
depolarizing (positive) current causesa decrease.While the depolarizingand hyperpolarizingcurrentswere differentin
this case, it is still clear that the latter is more effective in

increasingresponses
than the former is in decreasingthem.
Theseplots simply affirm observations
alreadymade, that
depolarizingand hyperpolarizingcurrentsare effectivein
alteringthesound-induced
response
magnitude,andthat the
effectsare asymmetrical(Russell, 1983;Nuttall, 1985;Dal-

AND DISCUSSION

A. Effect of current on the fundamental response

1. Results

Most resultspresentedin this paper are from a single

innerhair cell (MR056) from whichan unusuallycomplete
set of data could be recorded. These data are consonant with

informationgatheredfrom severalotherIHCs. The data

arepresentedprimarily asfrequencyresponse
functionsover
the relevantfrequencyrange.The bestfrequency(BF) of
the cell is 1000Hz at low sound-pressure
levels.The apparent bestfrequencyat 50 dB SPL, wheremostmeasurements
were taken, is shifted down to 800 Hz. This downshift of the

frequencyof maximumresponse
with increasingintensityis
well documented(Russell and Sellick, 1978;Dallos, 1985a)
and is probablyrelatedto a similar nonlinearphenomenon

los, 1986).

Somewhatmoreinformationmaybe gainedby an alternativeplottingschemeof magnitudepatternsif the peakdepolarizing and hyperpolarizingresponsesare given as a

functionof peaksound-pressure
level (Crawford and Fettiplace,1981;RussellandSellick,1983). To acknowledge
the
relation,but not identity, of the plotsto transducercharacteristics,we designatethem as pseudotransducer
functions
(PTF) (Dallos and Cheatham,1989b). In Fig. 3, suchplots
are shownfor the data includedin the previousfigure.The
rangeof soundlevelsis +_10-Papeak (91 dB SPL). The
form of these functions is somewhat

different from those

1982). The initial membranepotentialof the cell was -- 41

reportedin the literature,which tendto conformto the patternsof rectangularhyperbolas.In fact,for the morelimited

1637

P. Dallosand M. A. Cheatham:Polarizationof innerhair cells

seen in cochlear mechanics (Rhode, 1971; Sellick et al.,

J. Acoust.Soc. Am., Vol. 87, No. 4, April 1990

1637

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Frequency
0.2

-2 nA4ra'<zx)oOOOo

(kHz)

05

I
i

ill

IO

rr

02

0.

700 Hz

0.5

0.2

FIG. 4. Ac response
magnitudeasa
functionof stimulusfrequencyat a
constant,50-dB sound-pressure
level at the eardrum. Responsesare

MR05

shown for four current levels:zero,

-2, -1, and +lnA.

Sound Pressure (dBre 20/uPa)

rr 005

FIG. 2. Input-outputfunctionsfor the fundamentalac response

recorded

'0.02

50 dB
MR056

from a third-turn inner hair cell. Data are obtained from Fourier transforms

of theaveragedresponses
to tonebursts.Stimulusfrequencyis700Hz. Data
are shownfor threecurrentlevels,0, - 2, and d- 1 nA passedinto the cell
throughthe recordingelectrode.

rangeof + 1 Pa, suchan analyticaldescriptionis appropriate for these data (Dallos and Cheatham, 1989a,b). The

high-leveldeclineof the magnitudefunctionsseenin Fig. 2

is, of course,alsorepresentedin the plotsof Fig. 3, and it is
this declinethat makesthe rectangularhyperboladescription inappropriateoverthe full pressurerange.The asymmetry of effectiveness
of hyperpolarizingversusdepolarizing
currentsis amplyevidentin theseplots.An additionalasymmetry may be discernedhere that couldnot be from simple
magnitudefunctions.If the effectiveness
of extrinsiccurrent
is examinedat, say,the responsemaximum (at + 1Pa), it is
found that the effectis greaterupon the positivehalf-cycle
(72% increasefor -- 2 nA) than for the negativehalf-cycle
(47% increase). In other words, hyperpolarizationof the
cell by extrinsiccurrentmakesthe responsemore asymmetrical. To expressthis in differentterms,at 1 Pa, the peak-topeak responseincreases4.2 dB due to the -- 2-nA current,
while the dc componentincreases6.7 dB (the corresponding
numbersat 10 Pa are 4.1 and 7.2 dB). Theseplots are thus
providingus with the first indicationthat extrinsiccurrent
may affect different responsecomponentsin a nonequal

decreases(with depolarization)are obvious.Even cursory

examinationof the plots suggests
that low frequenciesare
influencedmore.Changesin response
magnitudeandphase
of the fundamentalac componentwith currentare shownin
Fig. 5. Examinationof thesechangesrevealsthe following
general pattern. Hyperpolarization causesa responseincreasethat is largestat low frequenciesand graduallydecreases
at higherfrequencies
with an apparentasymptoteat
the highestfrequencies.
Both low-frequencychangeand the
high-frequency
terminal portiondependon currentmagnitude.Similarbehavioris seenfor depolarization,but herethe
current causesa frequency-dependent
decrease.Hyperpolarization inducesa frequency-dependent
phaselag of the
fundamental responsecomponent, while depolarization
yieldsa phaselead. Thus it is clear that the frequencyresponsefunctionrevealedby the ac IHC receptorpotentialis
alteredby passingdc currentinto the cell. The presenceof a
constantasymptotecanbestbeappreciatedfrom theparallel
courseof the high-frequencyslopesof the ac magnitude

manner.

After lookingat thebasiccurrenteffectuponmagnitude

functions,frequencyresponse
functionsareprovidedin Fig.
4. Current levels used are + 1, 0, -- 1, and -- 2 nA. Graded

current-dependentincreases(with hyperpolarization) or
45

+1 nA

-2

Peak

Pressure

(Pa)

-4501
.I 0.2
I I I0.5
I IIlllI
Frequency (kHz)

FIG. 3. Samedataasshownin Fig. 2, but plottedaslinearresponse

magnitude( depolarizingandhyperpolarizing
peaksof theresponse)
versuslinear
peakpressurefrom averagedwaveforms.Positivepeaksare arbitrarily assignedto positivepressure.We designatetheseplotsas"pseudotransducer

FIG. 5. Differenceplotsbetweenvariouscurrentand no-currentconditions

asa functionof stimulusfrequency.Magnitudedataare derivedfrom the
plotsof Fig. 4, andphasedifferences
dueto currentarealsoshown.Includedin the figurewith interruptedlinesarethetheoreticalresultsobtainedin
theAppendixfor fittingthechangingmagnitudeandphasedataonthebasis

functions" in the text.

of the inner hair cell circuit model of Dallos (1984).

1638

J. Acoust. Soc. Am., Vol. 87, No. 4, April 1990

P. Dallos and M. A. Cheatham: Polarizationof inner hair cells

1638

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functions(Fig. 4). It is seenthat theseslopes,irrespectiveof

current, are approximately - 46 dB/oct.

hair cells results in active motion of the unrestrained

extrinsic

2. Discussion

Somebasic responsepropertiesof inner hair cells at

modestsoundintensityare revealedby the no-currentplots
of Figs. 1-4. Thesedata are in agreementwith thosepublishedby usandothersin thepast(Russelland Sellick,1978;
Dallos, 1985a, 1986). Characteristic features include a satu-

ratingnonlinearity,mostpronouncedat and aroundthe best

frequency,productionof depolarizingdc receptorpotentials
at all frequencies,
and bandpassresponse
for both ac and dc
components.

a. Current effects.In agreementwith previousdata

(Russell, 1983; Nuttall, 1985; Dallos, 1986), we find that

hyperpolarizationof the cell increasesall responses,

while
depolarizationdecreasesthem. The basicphenomenonis
consonantwith expectationsbasedon the Davis model of
hair cell action: Hyperpolarizationincreasesthe voltage
drop (electromotivedriving force) acrossthe cell'sciliated
apicalmembrane;depolarizationdecreases
it (Davis, 1965).
Also in agreementwith previousreportsis the asymmetryof
the effectof the extrinsiccurrent.Hyperpolarizationby a
certaincurrentincreases
all responses
morethandepolarization by the same amount of current decreasesthem. This
asymmetrydoesnot obviouslyfollow from simpleimplementationof the Davismodel.For example,thecircuitmodel proposed
by oneof us (Dallos, 1983) yieldsthe following
expression
for IHC receptorpotential(ei):

i [/3(Er q- E)yI ]/( 1 q-/3)2,

where/3is theshapefactor,representing
the ratio of resting
resistancesof basolateral and apical cell membranes,
/3 = Ro/R, Er isthescalamediarestingpotential,E isthe
electrochemicalpotential of the IHC's basolateralmem-

brane,andy/ is the fractionalresistance

change(due to
stimulation)of the aggregationof all transducerchannels.
The effectof electricalpolarizationby extrinsiccurrentis an
apparentchangein E: Negativecurrent makesit larger;
positivecurrentmakesit smaller.However,symmetricalincreaseand decreasein E yield symmetricalincreaseand
decreasein i,contraryto the data.The implicationis that
extrinsiccurrentaffectsnot onlythedrivingforcebut possi-

blytheshapefactor/3,or thefractionalresistance
changey/,
or both. Changesin the shapefactor imply that current
modifieseitherthe apicalor the basolateralresistances
of the
IHC membrane.Inasmuch as voltage-dependent
conductanceshave been reportedfor the latter (Kros and Crawford, 1988, 1989), thisis a reasonable
possibility.

Thealternative,
a current-dependent
changeinyI, suggestsan alterationof the input machineryof the IHC. This
could occurby either a changein the transducerchannels
dueto currentor by a modificationof the mechanicalinput
itself,conceivablyby someeffecton the cilia. The transducer
conductanceis probablynot voltagedependent(Corey and
Hudspeth, 1979; Ohmori, 1985; Holton and Hudspeth,
1986) but, dueto reciprocity,the gatingcompliancemay be
(Howard and Hudspeth, 1988). In fact, Assadet al. ( 1989)
haveshownrecentlythat electricalpolarizationof saccular
1639

J. Acaust. Sac. Am., Val. 87, No. 4, April 1990

hair

bundle.The physicalbasisthusexistsfor influencing

yi by
current.

One may be able to favor one of thesealternativesby

consideringthe effectof current on magnitudefunctions
(Fig. 2). We notedthat theselogarithmicplotsare translated along the vertical axis without a concurrenthorizontal
shift. The implicationis that current affectssomeelement
locatedafter the nonlinearitythat governsthe saturation
(Patuzzi and Yates, 1987). Saturation arises from two
sources. Nonlinear

cochlear mechanics controls saturation

aroundthebestfrequency,whilethecell'stransduction
processhasmajorinfluenceawayfrom the bestfrequencyof the
cell (Patuzzi and Sellick, 1983). Since the influence of cur-

rent uponmagnitudefunctionsis asdepictedin Fig. 2 for all

frequenciestested,it is parsimoniousto assumethat the effect of extrinsic current is on the basolateral membrane of

the cell, that is, after both of the aforementioned nonlinear

processes.We do not rule out the possibility,indeed the

probability, that current exertssomeeffecton both the ciliary mechanicsand the basolateralmembrane. As shown
below,eitherprocesscoulddescribesomesalientfeaturesof
the presentdata. For the sakeof parsimony,however,we
formulateour quantitativemodelin termsof the better understoodbasolateralmembraneprocess(seetheAppendix).
b. Frequency-dependent
changeof thefundamental. As
Figs.4 and 5 intimate, the currenteffecton the fundamental
componentof theacresponse
maybestbedescribed
asa gain
andphaselag (with negativecurrent) or lossandphaselead
(with positivecurrent). All magnitudechangesarefrequency dependentand mostpronouncedat low frequencies.
The
phasechangesappearlargestat midfrequencies.
Thesefrequency-dependent
effectsdue to the applicationof extrinsic
currentinto a hair cell havenot beenreported.Somereflection, however,indicatesthat they are not unexpected.
One can envisiondifferentmechanismswherebythe ac
receptorpotential would be nonuniformlyaffectedby current acrossfrequency.We havenotedabovethat a changein
eitherthe apicalor basolateralmembraneresistance,
acting
through the shapefactor/3 can affectthe response.Inasmuch as both apical and basalcell surfacescontain membrane capacitancesin parallel with the membrane resistances, changesin the latter inevitably alter the filter
propertiesof the cell membrane.From the vantagepoint of
an intracellularelectrode,both apicaland basalmembrane
filtersare low pass.The total filteringcharacteristicmay be
estimatedfrom membraneresistance
andcapacitance(Russell and Sellick, 1978; Dallos, 1984). It is thus conceivable

that the changesseenas a resultof extrinsiccurrent derive

from changingmembraneimpedance,i.e., a changingelectrical filter. This possibilityis examinedbelow. It is lessevident, but not a priori impossible,that the changingfilter is
relatedto the input ciliary mechanicsof the hair cell, i.e., a
changingmechanicalfilter. The latter is expectedto be a
high-passfilter, due to the viscousfluid couplingbetween
endolymphand cilia (Billone and Raynor, 1973;Dallos et
al., 1972). Changesin this filter would be affectedvia membrane voltageinfluencingciliary complianceor position.
This sortof behaviorhasbeensuggested
for outerhair cells
P. Dallas and M. A. Cheatham: Polarizationof inner hair cells

1639

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(Mountain et al., 1983), and its correlateshave been measuredin turtle cochlearhair cells (Crawford and Fettiplace,
1985) and in frog vestibularhair cells (Howard and Hud-

speth,1988;Assadetal., 1989).Thusit isof interestto seeif

the changingfilter patternsmaybe approximatedby simply
alteringthe cutofffrequencies
of simplefirst-orderlow- and
high-passfilters.
In Fig. 6, two examplesareconsidered.
First, we inquire
what changesare expectedif the cutofffrequency(frequency of the 3-dB down point and 45phaselag) of a low-pass
filter is shifted without any changein the attendantfilter
gain.In Fig. 6(a), it is assumedthat the shiftis 1 oct,from
500to 250 Hz. The changein magnitudeasa consequence
of

to be made. To obtain fits for the actual data, one must add
11.6 dB for the - 2-nA case,5 dB for -- 1 nA, and subtract

1.9dB for 4- 1nA. Thesenumbersareobtainedsimplyfrom

curve fitting. While the above exercise,utilizing a simple
first-orderfilter, is instructive,such a filter is not a good
analogof the hair cellcircuit.A morerealisticandcomplete
modelis consideredin the Appendix.
An alternativefitting methodis to assumethat it is the
cutofffrequencyof a high-pass
filter that is alteredby current..It is possibleto obtainreasonable
matchesof the data
with thisapproachaswell if the cornerfrequencyof a simple
high-pass
filter is shiftedfrom the 500-Hz valueat zerocur-

rentto 125Hz ( -- 2 oct) for -- 2 nA, to 250Hz ( -- 1 "bet)

such a shift is a loss that increases from zero dB at dc to 6 dB

for -- 1 nA, and to 650 Hz (0.38 oct) for + 1 nA. As before

at infinitefrequency.In general,the terminalattenuationis 6

dB timesthe frequencyshift in octaves.The corresponding
phaseshiftis a lag that is maximumbetweenthe two corner
frequencies.The conversemanipulation,shiftingfrom 250
to 500 Hz, would yield a mirror imagegain that increases
with frequencyfrom 0 to 6 dB and a phaselead.A comparison of thesepatternswith the data suggeststhat negative
currentmay yielda downshiftof the cornerfrequencywhile
positivecurrent,an upshift.
It is, in fact, possibleto obtainquite reasonablefits for
the experimentaldata by assumingcertainshiftsin the corner frequencyof a low-passfilter and providingcompensatinggain.Specifically,
it isassumed
that theno-currentcutoff
frequencyof our hypotheticallow-passfilter is 500 Hz (Ref.

somemagnitudecorrectionsare necessary
to obtaina good
match.Thesecorrectionsare relativelysmall:2.6 dB for the
- 2-nA case,0.4 dB for -- 1 nA, and -- 0.4 dB for + 1 nA.
Eitherthelow- or thehigh-pass
modelcanyieldtheconfigurationof amplitudeand phasechangesseen.Consideration
of the physicalnatureof a putativehigh-pass(ciliary mechanics)versuslow-pass(cell membrane)filter,alongwith
their locationcomparedto the nonlinearelement,as discussed
above,suggests
that the low-passmechanism
islikely
to be dominant in producing the large low-frequency
changes.
A knownlow-passfilter associated
with innerhair cells
is dueto the parallelcombinationof membranecapacitance
andresistance.
Voltage-dependent
conductances
in thecell's
basolateralmembranewould affectthe cutofffrequencyat
different membrane voltages.Specifically,depolarization

2) and that current shifts it to 177 Hz ( -- 1.5 oct) at -- 2

nA, to 300 Hz (- 0.75 oct) at -- 1 nA, and to 600 Hz
( 4-0.25 oct) at 4- 1 nA. In addition to the theoretical

changesthat resultfrom suchshiftsin gain,correctionsneed

(kHz)

Frequency
I

O.I
i

i i iii

, i

! I I ill

change
(dB)
o..

o.

-45t I

-90

,,
i

o
chnge(O!4
F-----__;__
, ,
(a)

90'

'

II

45
-:::::
0-

(b)

FIG. 6. Theoreticalplotsshowingchangesin magnitudeand phaseif the

cornerfrequencies
of simple(a) low-passand (b) high-passfiltersare shifted down by 1 oct (from 500 to 250 Hz). Top panels:frequencyresponse
plots(heavylines) andtheir asymptotes(thin lines)beforeandaftershifting.Secondpanelsfrom top:changesin magnitudedueto theshiftin corner
frequency.Note that, for the low-passcase,the shiftis a lossaccumulating
from0 to -- 6 dB asfrequencyincreases.
For thehigh-pass
case,thechange
is a gain decreasingfrom 4- 6 to 0 dB with increasein frequency.Second
panelsfrom bottom:phaseplotsbeforeand after shiftingthe cornerfrequency.Bottompanels:changein phasedueto shiftsin the cornerfrequency. Note that the phaseshift in both casesis a lag at midfrequencies.

1640

J. Acoust.Soc.Am.,Vol. 87, No. 4, April1990

should increase the conductance and raise the cutoff fre-

quency,while hyperpolarization
shouldresultin lowercutoff. Recall that hyperpolarizationincreasedthe low-frequencyresponsein our experiments.Loweringthe cutoff
frequencyof a low-passfilter [seeFig. 6(a) ] producedthe
correspondingprofile of frequency-dependent
changes.
Thus the mechanismwhereby extrinsiccurrent influences
the impedanceof the basolateralcell membraneand,consequently,itsfiltercutoff,produces
theappropriate
patternof
changes.In the Appendix,we includea morequantitative
treatmentof such changes.Basedon the model (Dallos,
1984), changesin filter functionare computedassuming
current-induced

alterations of the basolateral membrane re-

sistance,
R b. We showthat goodagreementmay be found
with the experimentalresults(comparedatapointsand interruptedlinesin Fig. 5). It is concluded
that thefrequencydependentchangesseenin the fundamentalresponse
componentcanbeaccounted
for asa consequence
of thechange
in the resistance of the IHC's

basolateral membrane. This

maybe expressed
differentlyby statingthat the controlling
influenceoverfrequency-dependent
response
changes
is the
current-inducedmodificationof the shape-factor
fl. We see
in theAppendixthat,fromitsnormalvalueoffl - 0.05,the
three current levelsused, -- 2, -- 1, and + 1 nA, alter fl to
values0.15, 0.09, and 0.042, respectively.

The high-frequencyasymptotesto the filter functions

reflectthe shift in the driving force,Er 4- E, as discussed
above.Theseasymptoticchanges,
consistent
with the simple
mechanoresistivemodel of transduction (Davis, 1965), are

P. Dallosand M. A. Cheatham:Polarizationof innerhaircells

1640

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the onesstudiedwith electricalpolarizationin the first-turn

recordingsat high frequencies(Russell, 1983; Nuttall,

frequencies,of the order of 25 dB for -- 2 nA. Thesedecreaseand appearto asymptoteat higher frequencies.In
1985).
orderto providereadycomparisonwith the fundamentalac
To summarize,current-inducedfrequency-dependent response
component,corresponding
changesin thismeasure
effectsseenin the fundamentalcomponentof ac receptor are alsoincludedin the figurerepresentedby the theoretical
potentialscannotbe due to electrodefilter artifacts.The efcurvescomputedin the Appendix[interruptedlinesin panel
fectsare characterizedby gain and phaselag with hyperpo(b) ]. It is observedthat the changesin the dc component
larization versuslossand phaselead with depolarization. exceedthosein the fundamentalat any corresponding
freNumericalresultscouldbe fit by appropriatelyshiftingthe
quencyfor both currentlevels.
cutofffrequencyof a low-passfilter and compensating
the
Our resultshowingthat electricalpolarizationhasa freresultinglosswith a constantgain. Modeling the current
quency-dependent
effectuponthe dc response
might appear
effectswith this simplechangein a low-passfilter cutoff
to be contraryto the findingof Nuttall ( 1985). He showed
frequencyprovidesthe heuristicexplanationof the phenom- that passingcurrent into IHCs produceda frequency-indeenon.A moreappropriatemodelingapproachtakesinto acpendentshift in the equipotentialresponse(sensitivity) of
count the behavior of the IHC as an electric circuit (Dallos,
the cell, as determinedfrom the dc receptorpotential.Nut1983, 1984). In the Appendix,we examinethe quantitative tall recordedfrom basalturn cellshavingvery highbestfreconsequences
of current-inducedalterationin the resistance quencies.Theseare well abovethe regionof frequency-deof the cell's basolateralmembrane (and, hence,of/3). It is
pendent changesseen in our work. The effectsthat we
shownthat excellentfits of the amplitudeand phasedata
observeasymptoteto a constantvaluesomewhatabove1000
may be obtained.
Hz. Nuttall's data wereobtainedon this asymptoticportion
of the function.

B. Effect of current on dc response

1. Results

2. Discussion

The asymmetryof tone-elicitedreceptorpotentialsis

accentuatedwith increasedhyperpolarizationof the cell. In
Fig. 7 (a), the dc responseis shownfor 0, -- 1, and -- 2 nA
as a functionof stimulusfrequency.We do not includeresponses
for the + 1-nA conditionbecausenot enoughdata
pointscouldbedeterminedwith certaintyto producea function. At 50 dB SPL, the dc response
is relativelysmallin the
third cochlearturn, and it becomesevensmallerduringthe
applicationof positiveextrinsiccurrent. Once again, the
impressionis that the effectof currentis greaterat low frequencies.This observationis substantiatedwith the aid of
Fig. 7 (b), wherechangesin the dc responses
areplotted.We
notethat quiteremarkablechangescanbe seenat the lowest

25

-2

25

20

20

os-

c I0

'- I0

o-

00.5
I

5O dB

O0)L

MR056
i

02

(a)

2-2

;,7-4-

! i Iiii

05

02

(b)

05

i
02

i ! ! iIlll
05

Frequency
(kHz) (c)

FIG. 7. Dc receptorpotentialdataderivedfromthesamematerialthatprovidedFig. 5. Panel (a): dc receptorpotentialmagnitudeas a functionof

frequencyat 0-, -- 1-, and -- 2-nA current levels.Panel (b): differences
between
thecurrentandno-current
dcmagnitudes
derivedfromtheplotsof
panel(a). Theoreticalfitsto changes
in theacfundamental
response
(interruptedlines)obtainedin theAppendixarealsoshownfor simplicityinstead
ofactualacdatapoints.Note thatthechangein dcresponse
greatlyexceeds
that of thefundamentalcomponent
at anyfrequency.Panel(c): samedata
asshownin panel(b) arereplottedfor comparison
withpredictions
based
ona square-lawnonlinearity(interruptedlines).The predictionissimplya
doublingof the decibelvaluesassociated
with the thin-line plots of
panel (b).
1641

J. Acoust. Soc. Am., Vol. 87, No. 4, April 1990

Normal innerhair cellsgeneratea positivedc receptor

potentialat all stimulusfrequencies
and levels(Russelland
Sellick,1978;Dallos, 1985a).This dc receptorpotentialis a
distortioncomponent,inasmuchasthe inputisa sinusoid.A
dc responsemay be generatedat any stageof signalprocessing in the cochleawhere the operationis describedby an
asymmetricalstimulus-response
transformation.Suggestionsfor suchasymmetrieshavebeenmadefor basilarmembrane motion (LePage, 1987), hair cell micromechanics
(Johnstoneand Johnstone,1966;Duifhuis, 1976), and hair
cell transduction(Flock, 1965;Dallos, 1973a;Weisset al.,
1974;HudspethandCorey, 1977;Crawfordand Fettiplace,
1981; Russellet al., 1986). It is likely that all transformations in the cochleaare nonlinearand asymmetric.Consequently,somedc componentmay be generatedat various
stepsof the signal'smodificationfrom pressureinput to
transmitter

release.

It is improbablethat currentpassedinto the cell would

affecteventsthat precedethe couplingof a mechanicalinput
into the IHC (Nuttall, 1985). Thus one may arguethat all
effectsseendueto extrinsiccurrentare a propertyof the cell
itself.Inasmuchas this currentproducesradicalchangesin
the dc response,it is unlikely that the latter could arise in
either mechanicalor micromechanicalpropertiesthat precedetransduction-related
processes.
Another line of reasoningleadsto thesameconclusion.It wasshownexperimentally that, at low frequencies,IHCs respondto the velocityof
basilar membrane motion (Dallos et al., 1972; Dallos,
1973b;Sellick and Russell, 1980;Nuttall et al., 1981;Dallos

and Santos-Sacchi,
1983). Theoreticalexplanationfor this
findinghasbeenprovided(Dallos et al., 1972;Billone and
Raynor, 1973;Freemanand Weiss,1988). This meansthat
dc componentspresentin basilarmembranemotion are effectivelydecoupledfrom stimulatingIHC cilia and will not
serveas direct inputs to this cell type, contraryto the assumptionsof LePage (1987, 1989). Of course,due to the
P. Dallos and M. A. Cheatham: Polarizationof inner hair cells

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firm contact between outer hair cell cilia and tectorial mem-

brane (Kimura, 1966), dc mechanicalinput would be very

effectivein stimulatingOHCs. The argumenthere is that
whateverdc responseappearsin the IHC receptorpotential,
it arises due to nonlinear

transformations

in this cell. Thus

the dc response,all-importantat high frequencieswherecycle-by-cyclereceptorpotentialsare negligible(Russell and

Sellick, 1978), is a propertyof the IHC itself,not a reflection
of rectificationoccurringprior to it.
Asymmetric nonlinear transformationsbetween two
variablestend to producedc responsecomponentsin proportion to the squareof the input amplitude.This is true for
polynomialnonlinearities(Dallos, 1973a) with rapidly decreasingcoefficients,as well as for hyperbolictangent-type
transformations(Boston,1980;WeissandLeong,1985). At
modestsoundlevels,the relationbetweenac and dc receptor
potentials,whether examinedwith changingsignallevel or
signal frequency, approximates square-law predictions
(Goodman et al., 1982; Russell and Sellick, 1983; Dallos,
1985a). A simple-square-lawnonlinearity would predict
that changesin the dc response(due to current) are twice as
large (in decibels)as in the fundamental.This square-law
predictionpresupposes
that the effectof the current isprior
to the nonlinearity and that the nonlinearity itself is unaffected.In Fig. 7 (c), we includesuchsquare-lawpredictions
for illustrativepurposes(dashedlines). It is apparentthat
the changein dc is considerablyin excessof the prediction.
The exaggeratedchangein dc responsedue to current
injectionis further illustratedin Fig. 8. The two panelsshow
ac and dc receptorpotential input-output functionsfor a
differentIHC in the sameexperimentalanimal. This cell is
approximately4 dB lesssensitivethan our other example.
Current-inducedchangesin the ac responseare similar to
those seen before, about 5-dB difference between the + 1

and -2-nA conditions.The correspondingchangein dc

response,however,is almost20 dB. This changeis so large
that, at higher soundlevels,there are no hyperpolarization
peaksin the ac response;
the entiresinusoidalswingis more
positivethan the cell'srestingmembranepotential(seeleft
panelof Fig. 1).
There are two readily apparentnonlineartransforma-

r 0,2

o.

do

o.

,oo

ioo

Sound Pressure Level (dB re 20

tionsaffectingthe receptorpotentialin hair cells.The firstis

the transducer nonlinearity, known to be asymmetrical
(Hudspeth and Corey, 1977; Boston, 1980; Crawford and
Fettiplace, 1981; Russellet al., 1986). The other may be
associated
with the voltage-dependent
conductanceresiding
in the cell's basolateral membrane.

Inasmuch

as the basola-

teral conductanceversustransmembranepotentialfunction
isnaturallytruncatedfor both the all-channels-open
and allchannels-closedsituations,it is inherently nonlinear. Since
at the restingmembranepotentialthe numberof openand
closedchannelsis unequal,it is also asymmetrical.Sucha
function can be derived from the conductance-data

of Kros

and Crawford (1988). From their data and from previous

assumptions
(Dallos, 1983), onecanestimatechangesin the
shapefactor/3 over the entire feasiblemembranepotential

rangein excess
of a hundredfold.
3 We havealreadynoted
that the frequencydependence
of the current-inducedac receptorpotentialchangeappearsto dependon modification
of the conductance

of the basolateral

cell membrane.

It is

then parsimoniousto assumethat the possiblenonlinearity

associatedwith this membranewould also governcurrentinducedalterationsin the dc response.Other considerations
alsosupportthis suggestion.
Assumethat the transducernonlinearity is unaffected
by current injection (Corey and Hudspeth, 1979;Ohmori,
1985; Holton and Hudspeth, 1986). Then, at a given frequency,a certaindc responseis producedby it, irrespective
of extrinsic current.

If there were no additional

nonlinear

effects,the changein this dc responsedue to currentwould

be determinedfor all stimulusfrequenciesby the low-frequencygainof the transferfunctionbetweencurrentandnocurrent conditions.As an example,we can obtainfrom the
computations
in the Appendixthat, for - 2 nA, thisgainis
10.1dB. Thus,for this hypotheticalcase,we wouldexpecta
changein dc responseof + 10.1 dB at all frequencieswith
- 2-nA current. However, the actual changeis frequency
dependent,rangingfrom almost25 dB at low frequencies
to
about 12 dB at high frequencies.The implicationis that a
nonlinearity, in addition to the transducerfunction, producesdc response,and that this nonlinearityis current dependent.If thisnonlinearitywouldfollow (or wouldbecoincidentwith) the frequency-dependent
transformationof the
fundamentaldue to current injection, then its effecthas to
accountfor the excessof about 15 dB gain at the lowest
frequencies
andabout3 dB at the highfrequencies.
Together
with the estimateddc gainfrom the transferfunctionof ---10
dB, the aboveyieldsthe rangeof 25- to 13-dBtotal changein
the dc responsebetweenlow and high frequencies
as in the
experimentalobservations,seenin Fig. 7 (b) and (c). We
tentatively concludethat the influenceof extrinsiccurrent
upon the voltage-dependent
conductanceof the basolateral
membrane is responsible for the frequency-dependent
changesseenin both fundamentaland dc responsecompo-

nentsof thereceptorpotential/
FIG. 8. Input-output functionsfrom a differentinner hair cell obtainedin
the electrodetrack prior to the one in which the other cell was located.
Membranepotentialof thiscellwas -- 20 mV. In theleft panel,theacmagnitudefunctionsare givenfor 0-, + 1-, and -- 2-nA conditions.Stimulus

frequencyis 700 Hz; thebestfrequencyof thiscellis 800 Hz. Right panel:

corresponding
dc receptorpotentialsat the three currentlevels.

1642

J. Acoust. Soc. Am., Vol. 87, No. 4, April 1990

Membranepotentialchangesoccurduringintracellular
recordingevenif not artificiallyinducedby polarizingcurrent. Receptor potential changescommonly accompany
suchvariations(Dallos, 1985b). One may surmisethat variationsin hair cell membranepotentialscantakeplacein the
P. Dallos and M. A. Cheatham: Polarizationof inner hair cells

1642

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intact cochleaaswell, presumablyresultingfrom pathological causes.Clearly, any changeaffectingthe stria vascularis

that the slopeof the regressionline is considerablysteeper

for the dc than for the fundamental.

Note that the rate of

or cochtear metabolism could cause alterations in membrane

changeof fundamentalmagnitudeis --0.15 dB/mV, con-

potentialsand,consequently,
in receptorpotentials.To illustrate theseinteractions,we presentinformation that is in
additionandcomplementaryto resultsfrom electricalpolarization experiments.A particularlyinformativeexampleis
shownin Fig. 9. Data aresummarizedherefor two recording
periods;duringthe first,the membranepotentialof the IHC
graduallyincreasedfrom -- 22 to -- 27 mV, while, during
the second,it held constant.During both periods,responses

trasted with

were measured to identical series of 14 sets of 800-Hz

tone

bursts (30 sampleseach) at 70 dB SPL. Magnitude and

phaseof the ac responsecomponentwere computedfrom
Fourier analysisof the averagedresponses.
The dc response
was obtaineddirectly from the averagedwaveforms.Individualdata pointsare shownin Fig. 9 asa functionof membranepotential (E), and two standarddeviationsare given
for the steadypotentialperiod.From the latter, it isapparent
that variationin response
is smallwhenthe E is constant.In
contrast,thereappearsa functionalrelationshipbetweenresponsemagnitudesand phaseand the membranepotential
when the latter changes.Least-squareregressionlineshave
beenfittedto eachdata cluster,and their equationsappearin

--0.33

dB/mV

for the dc. This difference in

slopebetweendc andfundamentalmagnitudes
hasbeentested for statistical significance(F ratios; Pedhazur, 1982,
Chap. 12), and it exceedsa criterionlevelof 1%.
We may surmisethat, inasmuchas the transducerfunction is unlikely to be voltagedependent,evenduring "naturally occurring" changesin membranepotential, it is the
nonlinearityof the basolateralmembranethat producesthe
excessvulnerabilityof the dc response.If thesefindingscan
be generalized, then one may argue that pathological
changes,evensubtleones,could have seriouseffectson the
high-frequencyresponseof the cochleawherethe output is
completelydependenton the IHC's dc receptorpotential.
There hasbeenonebrief reporton researchwith similar
concernsasthe presentwork. Mountainet al. (1989) noted
that, in basal-turninnerhair cells,usinglow-frequencystimuli, currentinjectiondid not alter the responsewaveformor
the relative second-harmonic

content. We assume that this

also signifiesthe constancyof the dc-to-acresponse.

ratio.
Our data indicatesignificantlygreaterchangesin either dc
or secondharmonicresponses
thanin the fundamentalcomthefigure,attached
totheactualregress.ion
line.Correlation ponent.Sincein all otherrespectsexaminedthusfar apical
coefficientsare r = 0.91 and 0.92 for the two magnitude and basal inner hair cellsbehavealike, this discrepancyis
surprisingand its causeis unclear.
functionsand r = 0.61 for the phasefunction.Theseare all
significantat the 1% level. Consequently,the changesin
magnitudeand phaseappearto be functionallyrelatedto E.
III. CONCLUSIONS
For our presentpurpose,the mostinterestingobservationis
The schematicdiagram of Fig. 10 may be helpful in
summarizingour results.Mechanicalinput to the cilia (en24dolymph flow, presumablydriven by differential motion
between
tectorialand reticularsurfaces)probablycontains
- fo=8.
all
orders
of nonlineardistortioncomponents.Potentialsre2O
cordedfrom the organof Corti fluid likely reflecta measure
18of this mechanicalinput, inasmuchasthesevoltagesdepend
16on outer hair cell currents.Thesepotentialscontaina rich
.
mixture of distortion products.Ciliary deflectionis high14passfiltered due to the propertiesof its hydromechanical
12excitation (Billone and Raynor, 1973;Freeman and Weiss,
1988). Cornerfrequencyis assumedto be 470 Hz (Dallos,
1984). Ciliary deflectionis transducedinto receptorcurrent

tic
=.6
-

flow into the cell with a nonlinear transformation (Hud-

- 90

a_ -8O

/ =.76,0.6E

''U

-20

-25
Membrane

Potential

-30

(mY)

FIG. 9. Changesin response

magnitudeandphaseduringa naturallyoccurring drift in the membranepotential (E) of an inner hair cell in the third
turn of the cochlea(animal DC045). During the recordingperiod, the
membranepotentialincreasedby approximately5 mV. During this time,
repeatedpresentations
of a seriesof tonebursts(800 Hz, 70 dB SPL) were
made. The responses
are comparedwith data obtainedfrom an identical
seriesof toneburstsduringa periodwhenthe membranepotentialwasinvariant.Theselatterdataaregivenasbarsrepresenting
two standarddeviations.Regressionlineswere fitted to the data during the variable-Eperiod
and theseare shown,alongwith their equations.
1643

d. Acoust.Soc. Am., Vol. 87, No. 4, April 1990

spethand Corey, 1977;Boston,1980;Crawfordand Fettiplace,1981;Russellet al., 1986). The transducernonlinearity further distortsthe alreadynonlinearsignal.
It isnot clearif thepotentialmeasured
by theintracellular electrodeclearly reflectseither the voltagedrop across
the cell's basolateralmembrane that is establishedby the
transductioncurrent itself, or the voltagedrop due to a secondarycurrentgatedby the receptorpotential.In nonmammalianhair cells,the latter caseprevails,the recordedvol-

tagedropbeingdominated
by K + andCa + currents
that
aresecondaryto the receptorpotential(CrawfordandFettiplace,1981;Lewisand Hudspeth,1983). As a consequence,
the transducernonlinearity is "hidden" under normal recordingcircumstances.
Considering
that in mammalianhair
cells,the receptorpotentialsshowsignificantrectification,
unlike normal turtle hair cells,it is possiblethat theseare
P. Dallosand M. A. Cheatham:Polarizationof innerhair cells

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duringdepolarization
(KrosandCrawford,
1988).6Second,

basolateral
membrane

nonlinear

IIR nonlinear

?N

',input
L

I' bill

N,,_I ,
~1200HzlI

' ciliary

receptor

potential

transduction

...................................
of

asa consequence
of the resistance
change,thelow-pass
electrical filter of the basolateralmembraneis altered.Hyperpo-

larization(increasedresistance)pushesthe filtercutofffrequencylower,whiledepolarization
increases
thebandwidth.
Thesefilter effectsare bestseenin changesof magnitudeand
phaseofthefundamental
response
to tones.Thechanges
can
beaccounted
for by usingthehair cellcircuitmodel(Dallos,

1984)shownin theAppendix.
7 In addition,by movingto
differentpointsonthenonlinearRo functiondueto extrinsic
current,differingamountsof distortioncomponents
(here
exemplifiedby de) are generatedin the cell'svoltageresponse.

distorted input

A hi.gh-pass
filtered

. '"""/ry
motion

ACKNOWLEDGMENTS

Researchwassupportedby NIH Grant No. NS08635.

We thank Dr. StephenEchteler,Dr. JonathanSiegel,and
the refereesof this paperfor their suggestions
aboutthe
manuscript.
APPENDIX

In the past,we haveevaluatedhair cell responses

in a
simplifiedcircuitmimickingcochlearelectroanatomy
(Dallos, 1973a, 1983, 1984). This was done with the aid of a

linear circuit in which the input consistedof variationsin

oneof the resistances.
In other words,a Davis-typecircuit
was considered (Davis, 1965). We have shown that varireceptor

ationof voltage(receptorpotential) appearing

at thenodeof

potential ]"nonlinear
Ibasolateral membrane

the circuit that simulates the IHC's

filter (current-dependent)

e...

FIG. 10.Top panel:blockdiagramindicatingpossible

locations
of various
sources
of nonlinearityandfiltering.Bottompanel:schematic
of IHC with
recordingelectrode.

dominatedby the transducercurrentand,thus,expressthe

transducer
nonlinearity.Alternatively,it isconceivable
that,
evenduringnormaloperation,the basolateralmembraneis
nonlinear and contributes to the rectification seen in the re-

sponse.Our previousargumentsthat hyperpolarization-inducedchanges

in thedc response
arelargerthanexpected
if
the only nonlinearitywereto precedethe basolateralmembranefilter suggestthis possibility.
We are assumingthat thereare two dominanteffectsof
polarizingcurrent.Theseare,first,the changingof theelectromotive"driving force" and, second,alteringthe resistance of the basolateralmembrane (Ro), and thus/3, by

influencingvoltage-dependent
channelstherein.
5 The
changein drivingforcecouldbe estimatedfrom the highfrequencyasymptotesof the changein fundamentalresponse.For plusandminus1-nA current,onecancomputea
decrease
of approximately5 mV andan increaseof approximately 4 mV in E.
In Fig. 10, the block "basolateralmembrane"symbolizes the latter secondclassof effectstwo ways. First is a

nonlinearchangein R o due to the current,with the resistanceincreasingduring hyperpolarization

and decreasing
1644

J. Acoust.
Soc.Am.,Vol.87, No.4, April1990

intracellular

electrode

locationcan be expressedas

-- ,8(El + Er )Y

(A1)

(1 -F//) (1
wheree; is the receptorpotentialamplitude,E is the biochemicalrestingpotentialoftheinnerhaircell,andEr isthe
endocochlear
potential.The quantity//wasdefinedas the
"shapefactor."It wasexpressed
astheratioof restingresistancesof basolateraland apicalcell membranes://=R o/
R. The input is in the form of parametricexcitation:
y; = (Ra - R )/R isthefractionalresistance
change,
with
R a beingthe instantaneous
valueand R the resting(no
stimulus) value of the resistanceof the cell'sapicalmembrane.When thefractionalresistance
changeissmall,asfor
smallinputs,onecansimplifythe aboveexpression:

e;...

-- ,8(El + ET)yI

.
(A2)
(] +fi)2
The computations
below are basedon this small-signal
expression
inasmuchas we are interestedin assessing
responses
to a moderate,
50-dBSPLinput.In thebestfrequency region,thesmall-signal
assumption
is probablyviolated;
however,the simplifiedanalysisdoesyieldqualitativelycorrectdescriptions
of the system's
behavior.The formulation
wasextendedto the generalcasewhen the cell membrane
containscapacitances
in parallelwith resistances
(Dallos,

1984).In thissituation,
theexpression
ford takestheform
ez (,j2rrf)

#q2rf) (E, +
[] +

r'q2rf)

P.DallosandM.A.Cheatham:
Polarization
ofinnerhaircells

(A3)
1644

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The frequency-dependent
quantitiesmaybeexpressed
asfol-

Let us now assumethat, due to passingcurrent into the

cell, we alter operatingconditions.The variablemostlikely
to be affectedby current is the basolateralmembraneresistanceRo. Assumethat Ro is alteredk fold. It is apparent
from the definitionof the quantitiesthat both/3 and ro will

lows:

/(j2rf) =/( 1 +j2rrfra )/( 1 +j2rfrb ),

(A4)

wherera and rb are the time constantsof apicaland basal

changek fold. Let us form the ratio of e (d2rrf)2and

e (d2rrf)l, wherethesubscript
2 refersto thechanged
condi-

cell membranes. Furthermore,

Y (j2rf) = ./(1 +j2rfr ).

tion (i.e., whenRo2 = kR b1) and subscript1 to the original

condition.Substitutioninto Eq. (3) yields

(A5)

(E12-+-Er)k(1 q-/)2(1+j2rrfkrb)[ 1 +j2rrf(rb +/3%)/(1 +/3)] 2

el ( Ell + ET) ( 1q-k/ )2( 1q-j2rrfrb) [ 1 q-j2rrfk( rb + fira) / ( 1 q-k/)]2

(A6)

Note that, dueto changingRo by a factorof k, a dc gainwas

time constantro and the shapefactor t9. In our previous

introducedin the amount of k(E12 +Er)(1 +/3)2/

(E l l q-Er ) (1 q- k/3)2. Further,thereis a frequencyde-

work (Dallos, 1983, 1984), we estimated these values. The

pendencedueto the changeandthisisexpressed

by a zeroat
f = 1/2rrkro ,
a pole at:
f2 = 1/2rrr,
a double zero at:

f3:

( 1 q-/)/2rr(%

q-/7'a ),

and a doublepole at:

f4 = ( 1 + ktg)/2rrk(r +/3ra ).
The two latter expressions
can be simplifiedbecause% and
rb are not independentquantities:r = ra/3C/Ca, where
C and Ca are the capacitancesof the basaland apical cell
membranes.The C/Ca ratio is the sameasthe ratio of surface areasof basolateraland apicalmembranes,which has
been obtained before. For third-turn inner hair cells, this

valueis 721/224 = 3.22 (Table I, Dallos, 1983). Using this

numericalvalue, we can obtain two final expressions
for f3
andf4:
f3 = ( 1 + t9)/8.23rb andf4 = ( 1 + k/3)/8.23kr.
We inquired if the computationalstructurepresented
hereisat all appropriate.
To thisend,thecomputations
were
performedfor a range of parametervalueswith the aid of
MathCAD (MathSoft, Inc. ) runningon a Compaq386 ATclone.As Fig. 5 indicates,it ispossibleto gaina goodquantitativematchfor bothmagnitudeandphasefor all threecurrent levels.The asymptoticvalue of Eq. (A6) for f o is
(E 12q- Er)/(E 11 q- Er). From curve fitting the data,
thesevaluesare approximately2.2 dB (for -- 2 nA), 0.3 dB
(for -- 1 nA), and - 0.4 dB (for + 1 nA). To fit the data,
we required parameters having the following values:
t9 = 0.05 and ro = 0.12 ms. The parameterk was assumed
to changewith currentlevel.The followingvaluesyield best
joint fit of magnitudeand phasedata:k = 3 (for -- 2 nA),
k=1.8

(for --1 nA) andk=0.85

(for +1 nA). Both

amplitudeand phasedata are acceptablymatchedby these

choices.

The arrangementof the pole-zerostructurein Eq. (A6)

is quite sensitiveto the choiceof the basolateralmembrane
1645

J. Acoust. Soc. Am., Vol. 87, No. 4, April 1990

shapefactor was obtainedfrom the geometryof the inner

hair cell, and a valueof 0.31 wasderived.We seethat fitting
of the currentdatarequiresa muchsmallert9,of the orderof
0.05. This implies that the imbalancebetweenapical and
basal membrane conductancesis greater than originally
thought. In other words,at normal membranevoltage,the
apicalmembraneresistance
is about20 timesthat of the basolateralmembrane,not 3 times. A further, interestingimplicationis that the biochemicalbattery that maintainsthe
cell's restingpotential has a lower value than what we assignedto it in the past.If t9 = 0.31, the endocochlear
potential Er = q- 70 mV and the measuredrestingpotential of
the IHC is E = -- 40 mV, then onecan computea valueof
-- 74.1 mV for E1 [ from Eq. ( 11) in Dallos, 1983]. In order
to obtain a/3 = 0.05, the value of E1 must be much lower:
-- 45.5 mV. 3
The value for the basolateral membrane's time constant

was derived beforeby assumingthat the basolateralmembranelow-passfilter wasresponsible

for the velocity-to-displacementtransitionof the IHC receptorpotentialwith increasingfrequency(Dallos, 1984). The cornerfrequencyfor
this changeis approximately470 Hz, yielding a ro = 0.34
ms. A secondtime constantof 0.13 ms, necessaryto fit the
data, was alsoincluded (Dallos, 1984). It is now apparent
that hydrodynamicprocesses
responsiblefor IHC stimulation, by themselves,possessthe necessarysimplepole that
governsthe velocity-to-displacement
transition (Freeman
and Weiss, 1988), probablyyieldingthe first time constant
of 0.34 ms. It is then more parsimoniousto acceptthe time
constantof ro = 0.12 ms, which is demandedby the curve
fitting, ascharacteristicof the IHC membrane.
lWehaveattempted
to obtainmeasures
ofthefrequency-dependence
of responsechangesdueto electricalpolarizationin six innerhair cells.In five
outof the six,the resultingpatternwasverysimilarto that shownin Fig. 4.
For example,the increasein the responseto the fundamentalfrom the nocurrent to the -- 1-nA conditionwas alwaysgreaterat low frequencies
than at higherones.The differencein changebetween280 Hz and 1.6kHz
for the fivecellswas:4.8, 3.0, 2.3, 1.9,and0.6 dB. No significantfrequency
dependence
wasfoundin onecell.

2Thechoice
of500Hz isnotarbitrary.Wehaveshownthatthird-turnIHCs
shifttheir modeof response
from velocitycontrolledat low frequencies
to
possiblydisplacementcontrolledat higher frequencies.The corner freP. Dallos and M. A. Cheatham: Polarizationof inner hair cells

1645

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quencyof thischangewasapproximately470 Hz (Dallos, 1984). The 500Hz choiceis simplya roundednumber.It maybe worth mentioningthat
the apparentshiftfrom velocitycontrolledto displacement
controlledresponsecan be due to a low-passfilter imposedeither by the viscoelastic
propertiesof cilia-tectoriumcoupling,or by the electricalpropertiesof
innerhair cell membrane.In eithercase,the approximately6-dB/oct rise
in IHC response,
in excess
of OHC response,
seenat thelowestfrequencies,

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J. (1983). "AC receptorpotentialsfrom hair
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would terminate at this cutoff (Dallos, 1984).

Dallos, P., Billone, M. C., Durrant, J. D., Wang, C. Y., and Raynor, $.

3Incorporation
of theKros-Crawford
dataintoourearliermodel(Dallos,
1983)yieldspredictions
asto thechanges
in response
thatmaybeexpected
with polarizationof the basolateralmembrane.We find that, asthe membranepotentialisalteredfrom0 to -- 60 mV, thecomputedshapefactor/,
changes
overa 130-foldrange,andthecomputedfundamental
acresponse
canchangeasmuchas20 dB. Thesecomputations
do not takefrequencydependent
effectsintoaccountthat wouldreducetheeffectiveness
of polarizationwith increasing
frequency,asdemonstrated
in the Appendix.Our
datafor thefundamentalcomponent's
changewithcurrentandfrequency
can be accommodated
by a modestoverallchangein/ of only threeand
one-half-fold.A directcomparisonwith Kros andCrawford'sin vitrodata
isdifficultsincewedid not measurethe actualchangein membranepotential due to polarization.
4Similar conclusionscan be drawn from our data about other even-order

harmoniccomponents,
well exemplifiedby the currentdependence
of the
secondharmonicresponse,

5Thethirdpossibility,
voltage-dependent
alteration
ofciliarystiffness,
cannot be ignored.It is, however,not treatedherein detail.

6Itisreasonable
toassume
that,inthesediscussions,
Rbrepresents
theslope
resistance.

7Inoursimplified
model,andin all discussions,
wehaveassumed
thatcurrent-inducedeffectiveresistancechangesin the basolateralmembraneare
sufficientto accountfor the observedphenomena.Another possibilityis
that polarizationcanchangethekineticpropertiesofbasolateralchannels,
with largereffectslikely to occurat lowerfrequencies.
It is possible
that a
modelcouldbe constructedon this basiswhich would yield an equally
satisfactory
fit of theexperimental
resultsastheonedetailedin the Appendix.

8Afterthesubmission
of thismanuscript,
startingfromsomewhat
different
considerations,
the samevaluesfor E l and/ wereproposedby Mountain
(1989).

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