Synaptic Physiology III

Question 1

Do all cells have approximately the same ionic composition, and are they all bathed in extracellular fluids with approximately the same ionic composition?

Answer 1

yes and yes

Question 2

What is the main determinant of the resting membrane potential of a cell?

Answer 2

Relative permeability to the different ions

Question 3

Why is the following statement wrong? “Hyperkalemia (elevated potassium ion concentration in the blood) makes the extracellular fluid very positive with
potassium ions, which hyperpolarizes neurons.”

Answer 3

Extracellular fluid is always electrically neutral. Hyperkalemia must be accompanied by a decrease in other cations, or an increase in some anion (or both).

Question 4

What is the effect of hyperkalemia on membrane potential of neurons? Why?

Answer 4

Depolarization. Hyperkalemia makes the concentration of potassium on the two sides of the membrane more nearly equal, which moves the potassium equilibrium potential towards zero. Because neurons are relatively highly permeable to potassium, the membrane potential follows, and the neuron depolarizes.

Question 5

How does the activity of the sodium pump contribute to membrane potential in a big cell with relatively few ion channels? In a cerebral cortical neuron with long, thin
processes (i.e., large surface area) and many active ion channels (i.e., action potentials)?

Answer 5

In big, tight cells, the sodium pump plays only a long term role, and blocking it has little or no immediate effect on membrane potential. In small, leaky cells with high fluxes of sodium, the pump’s role is more immediate (these cells fill up with sodium and lose potassium quickly if the pump is blocked).

Question 6

What is the function of APs?

Answer 6

To conduct electrical signals rapidly over long distances

Question 7

What cell types give APs?

Answer 7

Neurons and muscle fibers

Question 8

How are cells that give APs like cables?

Answer 8

They are cylindrical, and have a relatively low resistance interior that is covered by a insulator (the cell membrane), which is somewhat leaky, electrically speaking.

Question 9

What is the typical length constant (lambda, λ) of a cell that can give APs?

Answer 9

about 1 mm, which means that an applied voltage will decay to about 1/3 (1/e) in one λ , ~1/9 in 2 λ , etc.

Question 10

What is the function of the voltage-gated sodium channel in the AP?

Answer 10

It acts as a ‘booster station’, restoring the depolarization that would otherwise decay due to the leaky cable properties of the axon

Question 11

What are the two key components of any ‘booster station’?

Answer 11

An energy supply (to boost the decaying signal) and a detector (to know when to apply the boost)

Question 12

In a neuron, what is the energy source of the boost, and what is the detector?

Answer 12

The energy for the boost comes from the sodium ‘battery’ (the difference between the membrane
potential and ENa). The detector is the sodium channel activation gate (which is opened by the depolarization created by the approaching AP)

Question 13

How is the rising phase of the AP like an explosion (an example of positive feedback)?

Answer 13

Depolarization → Activation gates open → Sodium enters → more depolarization → …

Question 14

What is the role of the inactivation gate in

the sodium channel?

Answer 14

To make the channel stop conducting, even though the membrane is depolarized (i.e., the activation gate is still wide open)

Question 15

What is the role of the voltage-gated

potassium channel in the AP?

Answer 15

It speeds up repolarization, shortening the duration of the AP.

Question 16

What is the refractory period?

Answer 16

After giving an AP, an axon is less able to give another AP for a while

Question 17

What is the mechanism of the refractory period?

Answer 17

Inactivation gates are still closed and potassium channels are still conducting immediately after the AP finishes.

Question 18

How can a slow, steady depolarization (for
example, hyperkalemia) interfere with AP
generation?

Answer 18

The slow depolarization closes inactivation gates,

essentially knocking out those sodium channels

Question 19

Define the safety factor for AP

propagation.

Answer 19

Axons possess more than the minimal number of sodium channels required for conduction.

Question 20

What happens to the AP safety factor at an

axonal branch point? Why?

Answer 20

The safety factor is reduced, because the current produced by the membrane approaching the branch point is divided in two.

Question 21

How does myelin work?

Answer 21

It wraps the axon membrane, reducing membrane leakiness and (by virtue of increasing membrane thickness) reducing capacitance.

Question 22

Name several ways of increasing AP

conduction velocity in an axon

Answer 22

bigger diameter, less leaky surface membrane, higher density of sodium channels

Question 23

What role does the sodium pump play in

the AP?

Answer 23

None. Eventually, though, it must pump out the

sodium and reabsorb the potassium ions.

Question 24

How long does a nerve AP last?

Answer 24

about 1 ms

Question 25

How long does a ventricular muscle AP | last?

Answer 25

about 250 ms

Question 26

What are the 2 main channels that create | the cardiac AP plateau?

Answer 26

The ‘anomalous rectifier’ – this potassium channel closes with depolarization, and the voltage-gated calcium channels provide inward movement of this cation.

Question 27

How long does a skeletal muscle AP last?

Answer 27

about 1 ms

Question 28

When an axon is stimulated to threshold (away from its end), how many APs are created?

Answer 28

Two – they travel in opposite directions away from the stimulus site.

Question 29

When an axon is stimulated at 2 sites, and 4 APs are created, what happens to the 2 APs that collide with each other? Why?

Answer 29

They obliterate each other, because behind each AP the membrane is refractory.

Question 30

If the intracellular and extracellular fluids of an axon were switched, what would happen to the membrane potential? Could the axon give an AP? If so, would it be upside down?

Answer 30

The membrane potential would be positive (about +80 mV). This would close all inactvation gates, so it could not give an AP. (If in addition to switching solutions the membrane were inverted like a sock, then it could give an upside down AP).

Question 31

An extracellular recording of APs from a nerve trunk is smaller than an intracellular recording of an AP from a single neuron. Why?

Answer 31

The extracellular recording measures the tiny currents flowing in the extracellular space, which produce a potential change of only a millivolt or so.

Question 32

The amplitude of an extracellular recording of APs from a nerve trunk is not all-or-none, but is graded with stimulus strength. Why?

Answer 32

As the stimulus is turned up, more axons are recruited, giving a larger signal.

Question 33

How do calcium ions affect the action potential?

Answer 33

Ca++ binds to fixed negative charges on the outside surface of axons. This increases the (very, very localized) electric field across the membrane (hyperpolarization), which stabilizes activation gates in sodium channels in the closed position.

Question 34

What is the effect of reducing calcium ion concentration in the ECF?

Answer 34

Axons begin to fire APs spontaneously as Ca++ unbinds from surface charges, reducing the membrane electric field (depolarization), causing sodium channel activation gates to open.