Lecture 3 Active Membranes and Ion Channels Flashcards
Describe the structure of voltage-gated Na+ channels
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.
Which amino acids attribute the highly conserved charge of the selectivity pore of the VG Na+ channel?
Aspartate or Glutamate
Describe the mechanism by which Na+ passes through the Na+ channel pore
Asp and Glu lining the permeation pore extract the hydration shell surrounding Na+. The dehydrated Na+ passes through the channel in single file.
Describe the structure of the voltage-gated K+ channel
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
What is one structural difference between the VG Na+ and K+ channels?
The S4 voltage sensor region of VG K+ channels does not contain as many Ariginine residues, so it is activated more slowly.
What is used as diagnostic technique for demyelination of neuronal tissue?
Action Potential Conduction Velocity testing
Describe the general mechanisms for scorpion toxin, tetrodotoxin (pufferfish), and Karenia breves (red tide) toxin.
ScTx and TTX block at the external mouth of the channel pore. Karenia breves does not allow the channel to close.
Why does only dehydrated Na+ pass through VG Na+ channels?
Negatively charged amino acids line the channel pore. They pull H2O molecules from the hydration shell allowing Na+ to pass through.
What is the most common type of Ca2+ channel?
L type- CaV 1.x (first family)- dihydropyridine (DHP) sensitive
The T-type of Ca2+ channels has what characteristics?
CaV 3.x- low activation threshold; active at rest
What is phase 2 in ventricular action potentials?
Phase 2 is the plateau- slow Ca2+ inward (sodium can flow in as well, but mostly calcium) and minimal outward K+ current.
What phases does the sino-atrial action potentials consist of?
Phase 0- depolarization, inward Ca2+
Phase 3- repolarization, outward K+ current
Phase 4- slow depolarization, inward Na+ current, unstable resting membrane potential
What makes up the myelin sheath and what important property does it have?
Sphingomyelin; it has good insulating characteristics
What produces myelin in the CNS?
oligodendrocytes
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?
Saltatory conduction; it allows for cells to conserve energy & conduction velocity is increased
What is multiplle sclerosis (MS) and what are the symptoms?
MS is an autoimmune disease of the CNS caused by inflammatory processes that demyelinate axons. Symptoms include sporadic paresthesia (tingling) and motor dysfunction.
What is the specific sequence that creates the K+ channel canonical pore sequence?
Glycine Tyrosine Glycine Valine Threonine
What are the 5 subfamilies of the human voltage gated ion channel voltage sensors?
- Nav and Cav channels
- Two-pore channels (TPCs)
- Kv Channels
- Cyclic nucleotide-gated (CNG)
- Transient Receptor potential
What kind of specialized action potentials can exhibit a plateau phase?
Cardiac Ventricular Action Potentials
What is an example of a specialized action potential where some excitable cells fire rhythmically?
S-A Node (pacemaker)
What is an example of a cell that has a specialized action potential that occurs in peristalsis?
Enteric Pacemaker cells
What is an example of a cell that has a specialized action potential that occurs in the spinal cord or CNS?
Rhythmic oscillators
What are the action potential conduction velocities of small unmyelinated axons, small myelinated axons, and large myelinated axons?
Small unmyelinated axons = ~ 1 m/s
Small myelinated axons = ~3-15 m/s
Large myelinated axons = ~ 70 m/s
What happens in Wallerian Degeneration?
Type of axonal injury where axons and myelin deteriorate in peripheral nerves distal to the site of lesion. It takes about 2 weeks.
What do schwann cells in the PNS do when axonal injury occurs?
Release trophic factors taht induce axonal repair and remyelination
Can oligodendrocytes repair axonal injury? If yes, how? If no, why not?
No, oligodendrocytes in the CNS lack trophic factors causing limited ability for regeneration (effectively none)
What are the three classes of voltage-gated Ca2+ channels and where are they found?
- 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
