Lecture 3 Active Membranes and Ion Channels

Question 1

Describe the structure of voltage-gated Na+ channels

Answer 1

VG Na+ channels are single polypeptides (~2800 amino acids) with 4 homologous Domains (I, II, III, IV).
Each Domain has 6 α-helical spanning regions (S1-S6).
S4 contains the voltage sensor.
S5 - S6 linker forms the pore.

Question 2

Which amino acids attribute the highly conserved charge of the selectivity pore of the VG Na+ channel?

Answer 2

Aspartate or Glutamate

Question 3

Describe the mechanism by which Na+ passes through the Na+ channel pore

Answer 3

Asp and Glu lining the permeation pore extract the hydration shell surrounding Na+. The dehydrated Na+ passes through the channel in single file.

Question 4

Describe the structure of the voltage-gated K+ channel

Answer 4

4 subunits (~750 amino acids each).
4 separate gene products assemble on membrane
Heterogeneous assembly results in many VG K+ subtypes
Each subunit has 6 α-helical regions (S1-S6)
S4 - the voltage sensor
S5 - S6 linkers form the pore

Question 5

What is one structural difference between the VG Na+ and K+ channels?

Answer 5

The S4 voltage sensor region of VG K+ channels does not contain as many Ariginine residues, so it is activated more slowly.

Question 6

What is used as diagnostic technique for demyelination of neuronal tissue?

Answer 6

Action Potential Conduction Velocity testing

Question 7

Describe the general mechanisms for scorpion toxin, tetrodotoxin (pufferfish), and Karenia breves (red tide) toxin.

Answer 7

ScTx and TTX block at the external mouth of the channel pore. Karenia breves does not allow the channel to close.

Question 8

Why does only dehydrated Na+ pass through VG Na+ channels?

Answer 8

Negatively charged amino acids line the channel pore. They pull H2O molecules from the hydration shell allowing Na+ to pass through.

Question 9

What is the most common type of Ca2+ channel?

Answer 9

L type- CaV 1.x (first family)- dihydropyridine (DHP) sensitive

Question 10

The T-type of Ca2+ channels has what characteristics?

Answer 10

CaV 3.x- low activation threshold; active at rest

Question 11

What is phase 2 in ventricular action potentials?

Answer 11

Phase 2 is the plateau- slow Ca2+ inward (sodium can flow in as well, but mostly calcium) and minimal outward K+ current.

Question 12

What phases does the sino-atrial action potentials consist of?

Answer 12

Phase 0- depolarization, inward Ca2+
Phase 3- repolarization, outward K+ current
Phase 4- slow depolarization, inward Na+ current, unstable resting membrane potential

Question 13

What makes up the myelin sheath and what important property does it have?

Answer 13

Sphingomyelin; it has good insulating characteristics

Question 14

What produces myelin in the CNS?

Answer 14

oligodendrocytes

Question 15

Nodes of Ranvier have a high expression of VG Na+ and VG K+ channels; what is the ‘jumping’ on impulse from node to node called?

Answer 15

Saltatory conduction; it allows for cells to conserve energy & conduction velocity is increased

Question 16

What is multiplle sclerosis (MS) and what are the symptoms?

Answer 16

MS is an autoimmune disease of the CNS caused by inflammatory processes that demyelinate axons. Symptoms include sporadic paresthesia (tingling) and motor dysfunction.

Question 17

What is the specific sequence that creates the K+ channel canonical pore sequence?

Answer 17

Glycine
Tyrosine
Glycine
Valine
Threonine

Question 18

What are the 5 subfamilies of the human voltage gated ion channel voltage sensors?

Answer 18

1. Nav and Cav channels
2. Two-pore channels (TPCs)
3. Kv Channels
4. Cyclic nucleotide-gated (CNG)
5. Transient Receptor potential

Question 19

What kind of specialized action potentials can exhibit a plateau phase?

Answer 19

Cardiac Ventricular Action Potentials

Question 20

What is an example of a specialized action potential where some excitable cells fire rhythmically?

Answer 20

S-A Node (pacemaker)

Question 21

What is an example of a cell that has a specialized action potential that occurs in peristalsis?

Answer 21

Enteric Pacemaker cells

Question 22

What is an example of a cell that has a specialized action potential that occurs in the spinal cord or CNS?

Answer 22

Rhythmic oscillators

Question 23

What are the action potential conduction velocities of small unmyelinated axons, small myelinated axons, and large myelinated axons?

Answer 23

Small unmyelinated axons = ~ 1 m/s
Small myelinated axons = ~3-15 m/s
Large myelinated axons = ~ 70 m/s

Question 24

What happens in Wallerian Degeneration?

Answer 24

Type of axonal injury where axons and myelin deteriorate in peripheral nerves distal to the site of lesion. It takes about 2 weeks.

Question 25

What do schwann cells in the PNS do when axonal injury occurs?

Answer 25

Release trophic factors taht induce axonal repair and remyelination

Question 26

Can oligodendrocytes repair axonal injury? If yes, how? If no, why not?

Answer 26

No, oligodendrocytes in the CNS lack trophic factors causing limited ability for regeneration (effectively none)

Question 27

What are the three classes of voltage-gated Ca2+ channels and where are they found?

Answer 27

• L-type (CaV 1.x) is the most common; DHP-sensitive; important in use of Norvasc for congestive heart failure
• n-type (CaV 2.x) for neuronal/neurotransmission
• T-type (CaV 3.x) has low activation threshold; active at rest