Chapter 12: Nerve Physiology and Neurotransmitters

1. What are the processes that contribute the resting membrane potential (RMP) in nerves
and what precisely is the value of RMP in mV?
 The resting membrane potential exists because electrolytes are unequally distributed
between the ECF and the ICF
1. Three factors collectively determine the RMP:
a. Diffusion of ions down their concentration gradients through the
membrane.
b. Selective permeability of the membrane, allowing some ions to pass
more easily than others.
c. Electrical attraction of cations and anions to each other.
The resting membrane potential is -70 mV.

2. What is the concentration of sodium and potassium ions inside and outside the neuron at
RMP?
a. Potassium ions (K+) have the greatest influence on RMP because the plasma is
more permeable to K+ than to any other ion.
i. Many cytoplasmic anions cannot escape from the cell because of their size
or charge, so that diffusion of K+ out of the cell down its concentration
gradient leaves the ICF with a net negative charge.
ii. The negative ICF attracts K+ back into the cell, so that eventually
equilibrium is reached between concentration-driven diffusion and
electrical attraction; at this point, the net diffusion of K+ stops.
iii. At equilibrium K+ is 40 times as concentrated in the ICF as in the ECF.
iv. If K+ were the only ion involved, the RMP would be about –90 mV.
b. Sodium ions (Na+) also influence the RMP.
i. Na+ is 12 times more concentrated in the ECF than in the ICF.
ii. Although the resting membrane is less permeable to Na+, it does diffuse
down the concentration gradient into the cell and is attracted by the anions
of the ICF.

3. How much does the sodium potassium pump contribute to the RMP?
a. The Na+–K+ pump continually compensates for the leakage of Na+ and K+ into and
out of the cell.
b. For every 1 ATP consumed by the Na+–K+ pump, 3 Na+ are pumped out of the
cell and 2 K+ are brought in.
c. The Na+–K+ pump accounts for about 70% of the ATP requirement of the nervous
system and it works continually, which is why the nervous system consumes so
much glucose and oxygen.
d. The net effect of K diffusion outward, Na diffusion inward, and the action of the
Na–K pump is the RMP of –70 mV.

4. What is an action potential? Discuss the process in detail covering the events in order of
occurrence and the direction of ion flow.
  An action potential is a rapid up-and-down shift in membrane voltage produced by
voltage-regulated ion gates in the plasma membrane.
1. Action potentials occur only when there is a high enough density of voltage-
regulated gates; most of the soma cannot generate action potentials.
a. The trigger zone contains 350 to 500 voltage-regulated gates per μm2,
compared to 50 to 75 gates per μm2 in most of the soma.
2. If a local potential spreads all the way to the trigger zone and is still strong
enough, it can open the gates and generate an action potential.

3. The sequence of events in an action potential are as follows:

a. Na+ arrives at the axon hillock and depolarize the membrane as a local
potential.
b. The local potential must rise to the threshold (about –55 mV) to open
the voltage-regulated gates.
c. The neuron produces an action potential; the voltage regulated Na+ gates
open quickly, while K+ gates open more slowly, and the membrane
depolarizes further in a positive feedback cycle.
d. As the rising membrane potential passes 0 mV, Na+ gates are
inactivated and begin closing; by the time they all close, the voltage peaks
at about +35 mV.
e. By the time the voltage peaks, the slow K+ gates are fully open, and K+
now exits the cell, which acts to repolarize the membrane.
f. K+ gates stay open longer than Na+ gates, so slightly more K+ leaves the
cell than the amount of Na+ that entered; the membrane voltage drops to 1
or 2 mV more negative than the original RMP, a condition called
hyperpolarization or afterpotential.
g. Na+ diffusion into the cell and (in CNS) removal of extracellular K+ by
astrocytes gradually restore RMP.

5. What is a local potential?

It is a short range change in voltage caused by the incoming Na that diffuses for a short
distance along the inside of the plasma membrane and produces a current that travels
from the point of stimulation toward the cell’s trigger zone.

6. How are action potentials different than local potentials?

7. What is meant by the threshold for an action potential?
For anything to happen, local potential must rise to a critical voltage called the
threshold (typically about -55 mV) and is the minimum needed to open voltage-regulated
gates.

8. Describe how the concentration of voltage gated channels varies along the length of a
myelinated axon.
 In myelinated fibers, voltage-regulated ion gates are scarce in the myelin-
covered internodes (fewer than 25/μm2 compared with 2,000 to 12,000/μm2 in
nodes of Ranvier).
a. A nerve signal travels through an internode as Na+ diffuses down the
fiber under the axolemma; this flow is very fast but is decremental.
b. A node of Ranvier occurs every millimeter or less along the axon,
however, with an abundance of voltage-regulated gates.
c. When the diffusing ions reach a node, these gates are opened and a new
action potential is generated; this process of jumping from node to node is
called saltatory conduction.

9. What is depolarization?
It refers to any situation in which the membrane voltage shifts to a less negative value.

10. What is the refractory period, both absolute and relative?

The period of resistance to re-stimulation is called the refractory period
 Absolute refractory period: no stimulus of any strength will trigger a new
action potential
 Relative refractory period: possible to trigger a new action potential, but
only with an unusually strong stimulus.

11. What is salutatory conduction and how does it affect the conduction velocity of an axon?
 Process of jumping from node to node is called saltatory conduction.
 Voltage-regulated ion gates are scarce in myelin-covered internodes than at nodes of
Ranvier.
The only way a nerve signal can travel along an internode is for Na that enters at the
previous node to diffuse down the fiber under the axolemmaa very fast processnerve
fiber resist processconduction is decremental
Fortunately there is node of Ranvier every millimeter, where it is exposed to ECF and
there is abundance of voltage-regulated gates.
Internodes, saltatory conduction based on process that is very fast but decremental
Nodes, conduction is slower but non-decremental.
Since most of the axon is covered with myelin, conduction occurs mainly by fast
diffusion.

12. What are the different classes of neurotransmitters? What are the representative
neurotransmitters of each class?

13. How does GABA perform its inhibitory function?

a. GABA-ergic synapse employs γ-aminobutyric acid as its neurotransmitter; in an
inhibitory synapse:
i. The release of GABA by the presynaptic neuron and its binding to ion
gates is a similar mechanism as for cholinergic synapses.
ii. The GABA receptor, however, is a chloride channel, and when it opens,
Cl– enters the cell, increasing the negative membrane potential and
inhibiting firing.

14. Understand the basics of excitatory adrenergic synapse.

a. An adrenergic synapse employs norepinephrine (NE) as a neurotransmitter; its
receptor is not an ion gate but a transmembrane protein associated with a G
protein in a second-messenger system. (Fig. 12.23)
b. Binding of NE to the recetpro causes the G protein to dissociate from it.
c. The G protein binds to adenlyate cyclase, inducing it to convert ATP to cyclic
AMP (cAMP).
d. Cyclic AMP can induce several alternative effects inside the cell.
e. One effect is to produce an internal chemical that binds to a ligand-regulated ion
gate from inside the membrane, opening the gate.
f. Another is to activate preexisting cytoplasmic enzymes that affect metabolism.
g. Yet another is to induce genetic transcription, so that new enzymes are produced.

15. What are the methods by which signals are turned off that where stimulated by
neurotransmitters?
a. The cessation of action potentials in the presynaptic nerve fiber stop the release of
neurotransmitter.
b. The removal of neurotransmitter from the synaptic cleft is accomplished in three
ways.
 i. Diffusion. Neurotransmitter leaves the synapse and enters the ECF. In the
CNS, astrocytes absorb it and return it to neurons.
ii. Reuptake. The synaptic knob reabsorbs amino acids and monoamines by
endocytosis and breaks them down with monoamine oxidase (MAO).
iii. Degradation. The enzyme acetylcholinesterase (AChE) breaks down ACh
into acetate and choline, the latter of which is reabsorbed by the synaptic
knob.

16. What is the advantage for a neuron having a greater number of synapses?
It affords greater information-processing capabilities.

17. What is an EPSP? Which ions are involved?

Any voltage change in the direction that makes a neuron more likely to fire
Usually result from Na flowing into the cell and canceling some of the negative charge
on the inside of the membrane.

18. What is an IPSP? Which ions are involved?

Neurotransmitter hyperpolarizes the postsynaptic cell and makes it more negative than
the RMP, making the postsynaptic cell less likely to fire.
Produced by neurotransmitter opening ligand-regulated chloride gates, making the
cytosol more negative.
Less common way is to open selective K gates, increasing K diffusion out of the cell.

19. Understand temporal summation as compared to spatial summation in triggering

postsynaptic potentials?
Temporal Summation Spatial Summation
A single presynaptic neuron stimulates the Multiple inputs to the postsynaptic cell
postsynaptic neuron so intensely that its each produce a moderate amount of
EPSPs add up to threshold and make it fire stimulation, but collectively produce
enough EPSPs to add up to threshold at the
trigger zone and make the cell fire.

20. What is presynaptic inhibition?

Is the opposite of facilitation, a mechanism in which one presynaptic neuron
suppresses another oneused to halt unwanted synaptic transmission.

21. Understand the conditions of Alzheimer’s disease and Parkinson’s disease to the detail
covered in lecture and in your textbook
Alzheimer’s Disease:
a. One of first symptoms is memory loss, especially for recent events
i. Ask the same question repeatedly
ii. Reduced attention span
iii. Become disoriented and lost in previously familiar places
iv. Become moody, confused, paranoid, and combative
b. Loss ability to read, write, talk, walk and eat
 c. Death ensues from pneumonia or other complications of confinement and
immobility.
d. Diagnosis can be confirmed by autopsy
i. Atrophy of some of the gyri (folds) of the cerebral cortex and
hippocampus, an important center of memory.
ii. Nerve cells exhibit neurofibrillary tangles
iii. Intercellular spaces, there are senile plaques consisting of aggregations of
cells, altered nerve fibers and a core of beta amyloid protein—the
breakdown product of a glycoprotein of plasma membranes.
e. Three genes on chromosomes 1, 14 and 21 have been implicated in various forms
of early and late onset AD.
f. Treatment focuses on trying to halt beta amyloid formation or stimulate immune
system to clear beta amyloid from brain tissue.
i. AD patients show deficiency of acetylcholine and nerve growth factors.

Parkinson’s Disease
Also called paralysis agitans
A progressive loss of motor function beginning in the 50s and 60s.
c. c. Due to degeneration of dopamine-releasing neurons in portion of brain called the
substantia nigra.
d. d. Dopamine is an inhibitory neurotransmitter that normally prevents excessive
activity in motor center of brain called basal nuclei
1. Degeneration of dopamine-releasing
neurons leads to an excessive ratio of ACh to DA, causing
hyperactivity of the basal nuclei.
2. Suffer involuntary muscle contraction
3. Facial muscles become rigid
4. Speech slurred
5. Walks slowly with shuffling gait
g. Treatment with dopamine is ineffective because it cannot cross the blood brain
barrier
i. Precursor L-dopa does cross the barrier and used to treat PD
1. Relieves the symptoms but does not slow progression of disease.
ii. Newer Drug deprenyl, a MAO inhibitor that retards neural degeneration
and development of symptoms
iii. Surgical technique called pallidotomy used to quell severe
tremorsdestruction of small portion of cerebral tissue in area called
globus pallidus.
iv. Subthalamic nucleus and ventral intermediate nucleus are brain areas that
are targeted and involve either the destruction of tiny areas of tissue or the
implantation of stimulating electrodes.
a.