Action Potential

Question 1

Active signals in nerve cells

Answer 1

• a stimulating and a recording microelectrode are inserted into a neuron
• the lower panel shows potential recorded drops from zero to -65 mV
• current pulses are then passed by the stimulating electrode (upper panel), first hyperpolarizing (first two pulses)
• the second depolarizing pulse depolarizes the membrane to threshold producing a brief spike of depolarization called an action potential
• great depolarization produces more spikes at higher frequency

Question 2

Phases of the action potential

Answer 2

• rising depolarizing phase
• falling repolarizing phase
• the undershoot or afterhyperpolarization phase contains a refractory period during which it is not possible for the axon to have an action potential and then a relative refractory period when it required greater stimulation for the axon to produce another AP
• the undershoot then dissipates and the membrane potential returns to resting

Question 3

The rising depolarizing phase of the action potential

Answer 3

• experimental verification that Sodium is essential for the generation of AP
• lowered external NA+ results in smaller and slower action potentials
• sodium channels contribute to the depolarizing phase
• an important control is to return the external solution to normal

Question 4

Voltage sensitive mechanisms during the action potential

Answer 4

• action potentials are generated by three different voltage-sensitive mechanisms:
• 1) activation of Na+ conductance
  2) delayed activation of K+ conductance
  3) inactivation of Na+ conductance
• the undershoot of the membrane potential is due to open voltage gated K+ channels that gradually close and the membrane potential returns to the resting membrane potential

Question 5

Activation of Na+ conductance

Answer 5

• the voltage-depedent Na+ channels open and Na+ ions rush into the cell down their concentration gradient (inward current)
• accumulation of + charge inside and across the cell membrane
• depolarization of the membrane potential

Question 6

Delayed activation of K+ conductance

Answer 6

• after a delay the voltage-dependent K+ channels open
• K+ ions rush out the cell down their concentration gradient (outward current)
• reduction of + charge inside the cell membrane
• hyperpolarization of the membrane potential

Question 7

Inactivation of Na+ conductance

Answer 7

• voltage-dependent Na+ channels transition to a non-conductive state as voltage gated K+ channels begin to close
• the cell is refractory and does not fire action potentials in response to stimulation
• the inactivation gates then begin to open and the Na+ channels close

Question 8

Voltage Clamp Approach

Answer 8

• varied the membrane potential in squid giant axon to measure the changes in membrane conductance through voltage gated Na+ and K+ channels
• to interrupt the positive loop between membrane potential depolarization and the opening and closing of voltage gated channels
• the voltage clamp amplified injects a current into the cell that is equal and opposite to the current flowing through the voltage gated channels

Question 9

Changes in Na+ and K+ conductance

Answer 9

• the voltage clamp technique reveals two types of voltage dependent ion currents
• an early inward current (Na+)
• a late outward (K+) one
• the capacitive current supplies charge for the change accumulation across the membrane needed to step from a holding membrane potential to the new membrane voltage

Question 10

Drugs that change Na+ and K+ conductance

Answer 10

• using the voltage clamp technique it was shown that drugs that selectively block Na+ and K+ currents also selectively block the early and late currents
• TTX (tetrodotoxin) blocks sodium channels without affecting K+ channels- from puffer fish
• TEA (tetraethylammonium bromide) blocks K+ channels and is also an ACh receptor blocker

Question 11

Action potential propagation

Answer 11

• AP conduction required both active and passive current flow
• active- the gating of voltage gated channels and associated influx of Na+ current
• passive- depolarization wave the precedes the AP, positive ions entering axon via electrode or activated Na+channels passively move down the axon and neutralized negative membrane charges, decreasing the capacitive charge on the membrane and driving the membrane potential to threshold
• there is no passive current flow through the membrane only through channels
• passive positive ionic flow that neutralizes the negative charges on the inside of the membrane discharging the membrane capacitance and leading to sodium channel activation
• can only go the one direction because other side is inactivation

Question 12

Relative refractory period

Answer 12

-brief hyperpolarized membrane potential due to open resting and voltage gated K+ channels that ends when the voltage gated K+ channels close

Question 13

Summary changes in Na+ and K+ conductances

Answer 13

• Hodgkin and Huxley used the Voltage Clamp Technique to determine that Na+ and K+ conductances change with time and membrane potential
• APs are generated by four mechanisms: activation of Na+ conductance, activation of K+ conductance, inactivation of Na+ conductance, closing the voltage gated K+ channels
• APs first reverse the sign of the membrane potential at the peak (overshoot; gNa increase) and then hyperpolarize the membrane potential (undershoot; gKincrease) yielding a refractory period during which it is impossible, then harder (relative refractory) for the axon to produce another AP. Undershoot the dissipates (gKdecrease) and membrane potential returns to normal

Question 14

Myelination

Answer 14

• wrapping of glial cell membranes around the axon
• functionally equivalent to increasing membrane thickness by 100 times
• increases insulation which reduce leak of passive flow
• also decrease capacitance -> C= EA/d (d is total thickness, A= area)
• Na+ and K+ ions are localized

Question 15

Conduction in myelinated nerves

Answer 15

• fast passive potential between the nodes of Ranvier
• generation of action potential in the nodes (boosting stations)
• saltatory conduction: APs jump from node to node

Question 16

Nodes of Ranvier

Answer 16

• gap in myelin sheath
• separated by 1 or 2 mm
• contain full complement of Na+ and K+ channels
• generate action potentials

Question 17

Conduction velocity of nerves

Answer 17

• unmyelinated: 0.5 to 10 m/s

- myelinated ~150 m/s

Question 18

Multiple sclerosis

Answer 18

• a demyelinating disease, disrupts saltatory conduction slow and even blocking the transmission of nerve impulses in the CNS
• demyelination increases the capacitance of the membrane and thereby slows or even blocks AP propagation
• capacitance of node is 100-200 times greater than that of the intermode in normal nerve