Wagner - Propagation of the Action Potential Flashcards
A net integration yielding a suprathreshold depolarization at the axon hillock results in
activation of voltage-gated Na+ channels and triggers an action potential
What activates additional voltage-gated Na+ channels to propagate the action potential further down the axon?
the depolarization of plasma membrane segment due to the initial Na+ influx depositing positive charge
What can you expect if the axial resistance (Ra) of the cytoplasm is high?
a slower conduction velocity
Increasing axon diameter decreases _____, but also increases ____and_____ which reduces membrane resistance (Rm).
axoplasmic resistance (Ra) surface area and membrane capacitance (Cm)
Why does a decrease in Ra due to an increase in axon diameter have a greater functional impact?
because Ra varies inversely with the square of the axon diameter
What is the overall benefit of increasing the axon diameter?
longitudinal current flow (λ) and conduction velocity (Vc) both increase
What can you expect with a high Cm?
a slower conduction velocity
How does myelination decrease capacitance (Cm)?
By increasing the separation between extracellular and cytoplasmic sides of plasma membrane
Since the myelin sheath increases the insulation of the plasma membrane thereby increasing Rm, what counteracts this?
The Nodes of Ranvier interrupt the myelin sheath every 1-2mm and have dense clusters of Na+ channels to ensure that depolarizing inward Na+ current is produced allowing replication of the action potential at each node down the length of the axon
What do myelin and the Nodes of Ranvier increase?
λ=longitudinal current flow and Vc=conduction velocity
The pattern by which an action potential jumps from node to node is known as…
Saltatory Conduction
What are 3 general things to know about voltage-gated NA+ channels?
- rapidly activated by depolarization
- subject to rapid inactivation
- TTX sensitive
The Na+ channels are composed of an α & β subunit expressed in what ratio?
1:1 stoichiometric ratio
Which subunit consists of 4 linked homologous repeats each containing 6 transmembrane domains (Na+ channel)?
the α subunit
Which subunit can influence or modulate the amplitude of current and the kinetics of activation in Na+ channel?
the regulatory β subunit which is a glycoprotein with a single transmembrane domain
The Na+ channel ion pore comprises what transmembrane segments?
S5 & S6 and the intervening extracellular loop
What is the cause of TTX sensitivity in Na+ channel’s α subunit (subtypes 1-3 in CNS)?
a Glutamate residue at the 387th position (E387) and a Tyrosine residue at the 385th position (Y385) in extracellular loop between S5 & S6 of repeat 1
Of the 8 α subtypes why are α subtypes(1-3) 200x more sensitive (Na+ channels)?
because the α subtypes 1-3 have a Tyrosine residue instead of a Cysteine residue at position 385
What interactions and critical residues are responsible for Na+ selectivity in α subunit of Na+ channels?
interactions between S5 & S6 and the intervening extracellular loop, residues K1422 of repeat III and A1712 of repeat IV
Na+ channel activation is regulated by what 2 residues that serve as voltage sensors?
Basic residues Arginine and Lysine at every 3rd position in S4 of α subunit enable it to exist as an amphipathic helix
How does S4 of the α subunit respond to local depolarization in Na channels?
With a clockwise rotational conformation change that externalizes two positive charges resulting in gating current before channel opening
How is channel inactivation regulated in α subunit of NA+ channels?
Regulated by the hydrophobic latch within linking repeats III & IV formed by Isoleucine, Phenylalanine, and Methionine at positions 1488-1490
How many subfamilies of depolarization-activated, voltage-gated K+ (Kv) channels are there and how many subtypes of α subunits do they have?
there are 4 subfamilies with each one having up to 9 different subtypes
The α subunits of Kv contain 6 transmembrane proteins arranged as homotetramers and heterotetramers, but are not what?
They are NOT covalently linked together as four repeats
