3rd INTERNATIONAL CONFERENCE ON INFORMATICS, ELECTRONICS & VISION 2014

Analysis of Membrane
M Potential and Ion
Conccentration of Axon Celll
Akter Hossain Mohamm
mad Shafkat Islam Hedayet Ullah Muhammad Ahsan Ullah
Deparrtment of Electrical and Electronic Engineering
Chittaggong University of Engineering and Technology
Chittagong, Bangladesh
rafineee07@gmail.com

Abstract This paper provides a study of axon cell in terms of
membrane potential and ion conccentration using
Nernst/Goldman Simulator and MATLAB. Conventional cancer
detection only provides sufficient information n about growth of
cancer on human body, but there is little infoormation about the
growth of cancer in axon in terms of membran ne potential and ion
concentration. In a healthy cell the meembrane potential
preserves within range of -60 mV to -100 mV wherew negative sign
of the membrane potential indicates that the in nside surface of the
cell membrane is relatively more negative th han the immediate
exterior surface. The ratio of ion concen ntration of major
electrolytes, such as Potassium (K) and Sodiium (Na) ions (K+,
Na+) remains constant inside and outside of the t cell membrane.
Ratio of Potassium (K+) ions outside to inside a healthy cell is 20:
400 expressed by [Ko] : [Ki] = 20 : 400. The rattio of Sodium (Na+)
ions outside to inside a healthy cell is 440: 50 expressed
e by [Nao] :
[Nai] = 440 : 50. But whenever these cells becoome cancerous, the
value of membrane potential becomes around -15 mV because of
water flowing into the cells and Potassium m, Magnesium and
Calcium being lost from the cell interior and the ratio of
electrolytes are no longer sustained within desired values of
healthy cell. This paper provides ascendingg iteration process
using Nernst/Goldman Simulator and MATL LAB to achieve the
desired ion ratios at -15 mV membrane poteential in cancerous
cell.
Keywords- MATLAB, Nernst-Goldman Sim mulator, Axon cell,
Ion concentration, Ion transportation, Cancer.
I. INTRODUCTION
In cellular biology the term membrane trannsport refers to the
collection of mechanisms that regulate the passage
p of solutes
such as ions and small molecules throuugh stain proteins
embedded in them. The regulation of passsage through the
membrane is due to selective membrane permeability - a
characteristic of biological membranes whicch allows them to
separate substances of distinct chemical natuure. The separation
of charge across the membrane consistinng of thin cloud
positive and negative ions spread over thee inner and outer
surfaces of the cell membrane due to the liipid bilayer of the
membrane blocks the diffusion of ions. The charge separation
gives rise to a difference of electrical pootential across the
membrane, called membrane potential [1]]. The membrane
potential (Vm) is defined as, V V V
Where, Vin is the potential on the inside of thhe cell and Vout the
potential on the outside. The membrane pottential of a cell at
rest is called the resting membrane potenntial. All healthy
living cells have a membrane potential of appproximately -60 to
100mV. The negative signn of the membrane potential
indicates that the inside surfface of the cell membrane is
relatively more negative than the
t than the immediate exterior
surface of the cell membrane [2], [3]. In a healthy cell the
inside surface of the cell membrane
m is slightly negative
relative to its external cell membrane
m surface. When trans-
membrane potential of a healthhy cell is considered the electric
field across the cell membraane is enormous being up to
10,000,000 to 20,000,000 voltss/meter [2].
Healthy cells have high concenntration of potassium and a low
concentration of sodium [4], [55]. But because of water flowing
into the cells and Potassium, Magnesium
M and Calcium being
lost from the cell interior, canccerous cells have less membrane
potential [6], [7].
According to Charmana cell consists
c of four electrical zones
shown in Fig. 1 [2]. The ceentral zone contains negatively
charged organic molecules and maintains steady bulk
negativity. An inner positive zone exists between the inner
aspect of the cell membrane annd the central negative zone. The
inner positive zone is compoosed of a thin layer of freely
mobile mineral cations particuularly Potassium and according
to Hans Nieper a small amounnt of Calcium as well [2]. The
outer positive zone exists arouund the outer surface of the cell
membrane and consists of a denser zone of mobile cations
composed mostly of Sodium, CalciumC and a small amount of
Potassium. Because the conceentration of positive charges is
larger on the outer surface of o the cell membrane than the
concentration of positive chargges on the inner surface of the
cell membrane, an electrical potential exists across the cell
membrane. The outermost electrically negative zone is
composed of negatively chargeed sialic acid molecules that cap
the tips of glyco-proteins and glyco-lipids
g that extend outward
from the cell membranee like tree branches [2].
Fig.1 Discrete Electrical zones

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3rd INTERNATIONAL CONFERENCE ON INFORMATICS, ELECTRONICS & VISION 2014

A. The Electrical Properties of Cancer Cell usually maintain a constant radius), length (dendrites are
Few electrical properties of cancer cells are mentioned below- restricted to a small region around the cell body while axons
Cancer cells are less efficient in their production of can be much longer), and function (dendrites usually receive
cellular energy (ATP). signals while axons usually transmit them).
Cancer cells have cell membranes that exhibit different
electrochemical properties and a different distribution of
electrical charges than normal tissues [8], [9].
They also have different lipid and sterol content than
normal cells [2].
They have altered membrane composition and membrane
permeability, which results in the movement of
Potassium, Magnesium and Calcium out of the cell and
the accumulation of sodium and water into the cell [9]
[12].
Lower Potassium concentrations and higher sodium and
water content than normal cells [10], [11] causes change
in mineral content of the cell. Cancerous cells have lower
membrane potential than healthy cells because of increase
in the intracellular concentration of positively charged
Sodium ions and an increase in negative charges on the
cell coat (glycocalyx) [9].
Cancer cells exhibit both lower electrical membrane
potentials and lower electrical impedance than normal Fig. 2 Axon Cell
cells [12].
Since the membrane potential in a cancer cell is
consistently weaker than the membrane potential of a
healthy cell, the electrical field strength across the
membrane of a cancer cell is reduced. The reduction in
membrane electrical field strength will in turn cause
alterations in the metabolic functions of the cell.
In the resting phase normal cells maintain a high
membrane potential (Vm) of around -60 mV to -100 mV,
but when cells begin cell division and DNA synthesis the
membrane potential (Vm) falls to around 15 mV [2],
[13]. When a cell has completed cell division its
membrane potential will return back to normal.
According to Cone two of the most outstanding electrical
features of cancer cells is that they constantly maintain
their membrane potential (Vm) at a low value and their
intracellular concentration of sodium at a high
concentration [10][12].
Fig. 3 Ion concentration in an axon cell [1]
B. Axon Cell
Fig. 3 shows Graphical representation of axon cell having the
An axon, also known as a nerve fiber shown in Fig. 2 is a potassium channels. The potassium ions are colored blue, the
long, slender projection of a nerve cell, or neuron that sodium channels and the sodium ions are red, and the chloride
typically conducts electrical impulses away from the neurons channels and the chloride ions are green.
cell body. In certain sensory neurons (pseudo unipolar
neurons), such as those for touch and warmth, the electrical TABLE I. DISTRIBUTION OF THE MAJOR IONS ACROSS THE MEMBRANE
impulse travels along an axon from the periphery to the cell AT REST: THE GIANT AXON OF THE SQUID [1].

body, and from the cell body to the spinal cord along another Species of Concentration in Concentration in Equilibrium
branch of the same axon. Axon dysfunction causes many Ion cytoplasm (nM) extracellular fluid potential
inherited and acquired neurological disorders which can affect (nM) (mV)
both the peripheral and central neurons [14]. K+ 400 20 -75
+
An axon is one of two types of protoplasmic protrusions that Na 50 440 +55
extrude from the cell body of a neuron, the other type being Cl- 52 560 -60
dendrites. Axons are distinguished from dendrites by several Organic 385 - -
features, including shape (dendrites often taper while axons anions

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II. NERNST GOLDMAN SIMULLATOR

A. Nernst Equation
The Nernst equation named after the Germann physical chemist
who first formulated it, Walther Nernst givves a formula that
relates the numerical values of the concenttration gradient to
the electric gradient that balances it.
RT X
E
F
ln
X
(1)
Where, R is the gas constant, T is the tempeerature (in degrees
Kelvin), z is the valance of the ion, F the Farraday constant and
[Xo] and [Xi] are the concentrations of thee ion outside and
inside of the cell. At 25 Degree Celsius (rooom temperature),
RT
the value of is 25mV.
F
+
For K , since z = +1 and the concentrations inside and outside Fig. 4 Ion channel, equivalent circuit with
w current flow for Na, K and Cl ions
the squid axon is obtained from Table I. The relation between current and voltage provides a slope
V which is Conductance (K),
EK log 75 mV
m
I
For Na+, since z = +1 and the concentrrations inside and (3)
V
outside the squid axon is obtained from Tablle I. All of the passive K channels in a membrane can be lumped
EN
V
log 55 mV
m into a single equivalent elecctrical structure comprising a
battery (EK) in series with a connductor (gK).
For Cl-, since z = -1 and the concentrations inside and outside g K NK K (4)
the squid axon is obtained from Table I. Where, NK is the number of passsive K+ channels and K is the
V
EC log 60 mV
m conductance of a single K+ channnel.
The current through the K+ chaannel would be given by ohms
B. Goldman Equation law- iK K V (5)
The Goldman-Hodgkin-Katz equation, named in honor of In rest position, the net currennt must be zero; otherwise the
separation of positive and negative charges across the
American David Goldman and the British NobelN laureates Sir membrane would change, cauusing Vm to change. Therefore,
Alan Hodgkin and Sir Bernard Katz; frequentlyf simply INa is equal and opposite of IK.
referred to as the Goldman equationcalcullates an estimated
membrane potential that reflects the relativve contributions of IN IK Or,
O IK IN 0 (6)
the chemical concentration gradients and relative
r membrane For the calculation of INa annd IK, the individual potential
permeability for K+, Na+ and Cl. differences across the Na+ and K+ branches of the circuit.
The Goldman equation is, In case of Na+ branch, the total potential difference is the sum
RT PK K O PN N O PC C
V ln (2) of the potential differences acrooss ENa and across gNa.
F PK K PN N PC C O IN
This equation applies only when Vm does d not change. So, V EN (7)
N
According to this equation the greater the concentration
c of a Similarly, For the K+ conductannce branch,
particular ion species and the greaterr its membrane IK
V EK (8)
permeability, the greater its role in determinning the membrane K
potential. When permeability to one ion is exceptionally
e high, So the equation of current is,
the Goldman equation reduces to the Nernstt equation for that IN gN V E N , IK g K V EK (9)
ion. These equations illustrate, thhe ionic current through each
The data for the membrane at rest could bee fit accurately by conductance branch is equal too the conductance of that branch
the Goldman equation using the following permeability ratios- multiplied by the net electrical driving force.
PK: PNa: PCl = 1.0: 0.04: 0.45 According to the equation, IK IN 0,
However, the variation of Vm withh external ionic V gN gK EN gN EK g K
concentrations was fit best if a quite different set of By solving the above equation Vm is,
permeability ratios were assumed: PK: PNa: PCl = 1.0: 20: 0.45 EN N EK K
V (10)
A cell membrane has three types of ion transfer path like K+ N K

channel, Na+ channel and Cl channel. The difference of ion For normal position, Vm = -69mmV [1].
ratio between inner and outer side of cell crreates a membrane The real resting membrane has open channels not only for Na+
potential. Similarly conductance can also bee found due to the and K+ but also for Cl. So thhe equation of Vm including the
flow of electrolytes. For a single K+ channel can be conductance pathway of Cl
EN N EK K EC C
represented as a conductor or resistor (conduuctance, ). V (11)
N K C

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3rd INTERNATIONAL CONFERENCE ON INFORMATICS, ELECTRONICS & VISION 2014

TABLE II. AVERAGE CONCEENTRATION LEVELS OF GENERIC CELL, SKELETAL MUSCLE, SQUID AXON, RED CELL

Average Concentration Levels: Averagee Concentration Levels: Average Concentration Levels: A

Average Concentration Levels:
Generic Cell S
Skeletal Muscle Squid Axon Red Cell.
Ion
Intra Extra Membrane Intra Extra Membrane Intra Extra Membrane In
Intra Extra Membrane
Permeability Permeability permeability permeability
(P) (P) (P) (P)
K+ 120 4.5 100 150 4.5 100 400 20 100 1
140 4.5 100

Na+ 15 145 5 12 145 1 50 440 1 11 145 54

Cl- 20 116 10 4.2 116 1000 40 560 10 80 116 21

Concentrations for K+, Na+, and Cl for fourr cell different cell and the concentrations inside and
a outside the squid axon in are
types: (1) Generic cell; (2) Skeletal musclee; (3) Squid giant shown Fig. 5.
axon; and (4), Red cells are shown in Table II.
I V
EK log 1.3 mV (12)
So, the total conductance, g g N g K g C
The value of total conductance is 13 X 10-6 S.
S
III. ME T H O D O L O G Y
The main goal of this study is to find the raatio of electrolytes
(Na+, K+) inside and outside of the Axon cell. The
Nernst/Goldman Simulator and MATLAB arre used to find out
the ratio.
A. Ion Concentration
For each ion (K+, Na+ and Cl) a slider is provided
p to adjust
one of three parameters. Two of these sliders control the
intracellular and extracellular concentratioons of the ion in Fig. 5 K Ion concentration inside and outside
o of the cell using Nernst Equation
and Membrane potential for K ion conncentration inside and outside of the cell
question, and these can be varied between vaalues of 1 mM and using Nernst Equation
600 mM. The default values are: for K+, 100 mM out and 100 For Na+, since z= +1 and the cooncentrations inside and outside
mM in; for Na+, 100 mM out and 10 mM inn; and for Cl, 100 the squid axon are shown in Figg. 6.
mM out and 10 mM. V
EN log 7.7mV (13)
B. Temperature
In addition to controls associated with K+, Na+ and Cl-, there is
a slider for controlling the temperature. Although the slider
reports values in degrees C, temperature values used for
calculation of Nernst or Goldman potentiaals are in degrees
Kelvin. Selected temperature is 25 C as like room
temperature.
C. RT/F
''R'' is the gas constant, and in this applicatiion has a value of
8.314 Joules.K-1mole-1, T is the temperature in degrees
Kelvin, F is the Faraday constant (the amount
a of electric
Fig. 6.Na ion concentrations inside and outside of the cell using Nernst
charge in one mole of electrons) has a value of 96,485 Equation and Membrane potential for Na ion concentration inside and outside
coulomb mole-1. For room temperature 25 C, RT/F =25.217. of the cell using Nernst Equation
For Cl-, since z = -1 and the conncentrations inside and outside
D. Iteration Process Using MATLAB
the squid axon are shown in Figg. 7.
Using Nernst-Goldman equation, the ratio off ions in cancerous V
EC log 60mV (14)
cells can be found easily. Since the equilibrrium voltage rises
to -15mV from -67.45mV; -67.45mV is thee average value of Concentration of Cl ion has a little effect when cells become
equilibrium voltage (Vm). Range of Vm is -60 to -100 mV. cancerous. For that reason, ionns ratio and membrane potential
When a cluster of cell become cancerous, sinnce z= +1 for K+, for Cl ion is constant.

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3rd INTERNATIONAL CONFERENCE ON INFORMATICS, ELECTRONICS & VISION 2014

N
(16)
N
Table III represents the output of the ratio of K and Na ion
when cells become cancerous for both MATLAB and
SIMULATOR.

TABLE III. RATIO OF K AND NA ION IN A CANCEROUS CELL

Ratio MATLAB SIMULATOR

[Ko] : [Ki] 191 : 229 190 : 230

Fig. 7 Cl ion concentration inside and outside of the cell using Nernst
Equation and Membrane potential for Cl ion concentration inside and outside
of the cell using Nernst Equation
IV. RESULTS AND DISCUSSION
In the resting phase, normal cells maintain a membrane
potential (Vm) of around -60 mV to -100 mV, but when cells
begin cell division and DNA synthesis, membrane potential
(Vm) reaches approximately -15 mV. When a cell completes
its division, membrane potential returns to normal value of -60
mV to -100 mV of resting phase. At resting phase the ratio of
ions is constant, but when cells become cancerous, this ratio
no longer remains the same. This thesis provides the ratio of
ions- especially of Sodium and Potassium ions, through
iteration process using MATLAB and also from the Nernst-
Goldman Equation Simulator. It has been found that there is
no vital change in ion concentration of chlorine in any
condition hence it acts as a neutral element.
Determining the ratio of sodium and potassium ions will
accelerate the process of cancerous cell detection. Ratio of
potassium and sodium at resting phase is [Ko] : [Ki] = 20 : 400
and [Nao] : [Nai] = 440 : 50. And at aberrant condition when it
becomes cancerous the ratio is [Ko] : [Ki] = 191 : 229 and
[Nao] : [Nai] = 269 : 221, is found through iteration process in
MATLAB. And when The Nernst-Goldman Equation
Simulator is used then the ratio becomes [Ko] : [Ki] = 190 :
230 and [Nao] : [Nai] = 270 : 210. For detection of normal and
cancerous axon cells, this process may give instantaneous and
better results. This hypothesis is the entrance of a neophyte
cancerous cell detection notion.
A. Results Obtained from MATLAB
Number of steps, i = 172
Membrane potential, Vm (i) = -14.8382
Value of potential for Na, Ena = 4.268e-008
Value of potential for K, EK = -7.88021e-007
Number of K ions outside the cell membrane, ko = 191
Number of K ions inside the cell membrane, ki = 229
Number of Na ions outside the cell membrane, nao = 269
Number of Na ions inside the cell membrane, nai = 221
B. Results Obtained from Simulator
When the potential of K+, EK = -1.3 mV, then the ratio of
outside and inside ions of potassium found by the simulator is,
K
(15)
K phosphorylating (glucokinase) activities in a range of tumor cell lines
+
When the potential of Na , ENa = +7.7 mV, then the ratio of
outside and inside ions of potassium found by the simulator is,
[Nao] : [Nai] 269 : 221 270 : 210
V. CONCLUSION
This study provides the information for the worst situation, in
a cancerous cell on the basis of membrane potential and ion
concentration which may provide instantaneous and better
results. Iteration process using Nernst/Goldman Equation
Simulator [15] as well as MATLAB provides a good
understanding of the expected ratio of electrolytes. This novel
process of detection of cancer may introduce versatile
opportunities for researchers and a revolutionary change can
occur in medical science especially in the section of detection,
analysis and treatment of diseases.
ACKNOWLEDGMENT
All eulogize to Allah the All Mighty, the most genial, most
gracious, and most munificent.
REFERENCES
[1] A. L. Hodgkin and W.A.H. Rushton, The electrical constants of a
Crustacean Nerve Fibre, Proceedings of Royal Society of London.
Series B, Biological Sciences, vol. 133, no. 873, pp. 444-479, December,
1946.
[2] S. M. D. Haltiwanger, The Electrical Properties of Cancer Cell,
http://www.royalrife.com/haltiwanger1.pdf, 2013.
[3] M. Garnett, First Pulse: A Personal Journey in Cancer Research, New
York, 2001.
[4] C. D. Cone, Variation of the transmembrane potential level as a basic
mechanism of mitosis control, Oncology, vol. 24, no. 6, pp/ 438-370,
Feb. 1970.
[5] C. D. Cone, The role of surface electrical transmembrane potential in
normal and malignant mitogenesis, Annals of New York Academy of
Sciences, vol. 238, no. 1, pp.420-435, Oct. 1974.
[6] J. C. Cure, Cancer an electrical phenomenon, 1991.
[7] J. Gold, Proposed treatment of cancer by inhibition of
gluconeogenesis, Oncology, vol. 22, no. 2, pp. 185-207, 1968.
[8] E. J. Ambrose, A. M. James and J. H. B. Lowick, Differences between
the Electrical Charge carried by Normal and Homologous Tumour
Cells, Nature., vol. 177, no. 4508, pp. 576-577, Mar. 1956.
[9] M. Board, A. Colquhoun and E. A. Newsholme, High Km glucose-
and inhibition of rates of tumor growth by the specific enzyme inhibitor
mannoheptulose, Cancer Research, vol. 55, no.15, pp.3278-3285, Aug.
1995.

978-1-4799-5180-2/14/$31.00 2014 IEEE

3rd INTERNATIONAL CONFERENCE ON INFORMATICS, ELECTRONICS & VISION 2014

[10] H. F. Acevado, J. Y. Tong and R. J. Hartsock, Human chorionic [13] F. W. Cope, A medical application of the Ling Association-Induction
gonadotropinbeta subunit gene expression in cultured human fetal and Hypothesis: The high potassium, low sodium diet of the Gerson cancer
cancer cells of different types and origins, Cancer, vol. 76, no. 8, pp. therapy, Physiological Chemistry and Physics, vol. 10, no. 5, pp. 465-
1467-1475, Oct. 1995. 468, 1978.

[11] W. R. Adey, Physiological signaling across cell membranes and
cooperative influences of extremely low frequency electromagnetic
fields, in Biological Coherence and Response to External Stimuli. Berlin
Heidelberg: Springer, 1988. pp. 148-170.
[12] R. C. Niemtzow, Transmembrane Potentials and Characteristics of
Immune and Tumor Cells, Boca Raton, Florida: CRC Press, 1985.
[14] A. Chedotal, G. Kerjan and C. Moreau-Fauvarque, The brain within the
tumor: new roles for axon guidance molecules in cancers, Cell Death &
Differentiation, vol. 12, no. 8, pp. 1044-1056, Aug. 2005.
[15] Dr. Stephen Wright, The Nernst-Goldman Simulator. Copyright 2012.
http://www.nernstgoldman.physiology.arizona.ed

APPENDIX: CALCULATION FOR ION TRANSFER RATIO

EN N EK K EC C RT X
The equation of Membrane potential, V and Equation of Potential due to Ion, E ln
N K C F X
From the above equations, The value of Vm has been calculated for different combination of values of [K0+], [Ki+], [Na0+] and
[Nai+] to get desired value of -15 mV of cancer affected cells. It has been found from MATLAB that the desired result of -15 mV
is obtained when [K0+] =190, [Ki+] =230, [Na0+] =270 and [Nai+] =210.

Appendix Table : Steps of calculation Sample Number

Sample [K0+] [Ki+] [Na0+] [Nai+] Vm (mV)
Number
1 20 400 440 50 -67.45
2 25 395 435 55 -62.99
3 30 390 430 60 -59.13
4 35 385 425 65 -55.99
5 40 380 420 70 -53.25
6 45 375 415 75 -50.79
7 50 370 410 80 -48.58
8 55 365 405 85 -46.55
9 60 360 400 90 -44.67
10 65 355 395 95 -42.92
11 70 350 390 100 -41.28
12 75 345 385 105 -39.73
13 80 340 380 110 -38.26
14 85 335 375 115 -36.85
15 90 330 370 120 -35.51
16 95 325 365 125 -34.23
17 100 320 360 130 -32.99
18 105 315 355 135 -31.79
19 110 310 350 140 -30.63
20 115 305 345 145 -29.50
21 120 300 340 150 -28.41
22 125 295 335 155 -27.34
23 130 290 330 160 -26.29
24 135 285 325 165 -25.27
25 140 280 320 170 -24.27
26 145 275 315 175 -23.29
27 150 270 310 180 -23.32
28 155 265 305 185 -21.37
29 160 260 300 190 -20.43
30 165 255 295 195 -19.49
31 170 250 290 200 -18.58
32 175 245 285 205 -17.66
33 180 240 280 210 -16.76
34 185 235 275 215 -15.86
35 190 230 270 220 -14.97

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