Voltage Gated Sodium Channels (VGSCs) Practice Flashcards

This set of flashcards covers the structure, function, and pharmacology of Voltage Gated Sodium Channels (VGSCs) based on the lecture material.

Voltage Gated Sodium Channels (VGSCs)

Proteins of a neuron that generate the rising phase of the action potential and are also involved in persistent depolarizations, dendritic boosting, and cell-cell adhesion.

Alpha subunit

A single protein comprising four domains that forms a fully-functioning ion channel; at least nine different types ($Na_V1.1$ to $Na_V1.9$) are coded in the human genome.

Beta subunit

An auxiliary protein that is not channel-forming but is critical for controlling the localization and biophysical characteristics of the alpha subunit.

$S4$ helix

The transmembrane segment within each domain that acts as a voltage sensor; it is mobile and rich in positively charged amino acids.

$S5-S6$ helices

The helical transmembrane segments that form the central pore of the sodium channel.

Inactivation gate

A specific loop located between Domain III ($DIII$) and Domain IV ($DIV$) of the alpha subunit that is responsible for fast inactivation of the channel.

IFM sequence

A hydrophobic sequence consisting of isoleucine, phenylalanine, and methionine that attaches to a binding site at the face of the inner pore to block sodium flow during inactivation.

Inactivated state

A state in which the channel pore is open but not conducting because the inactivation gate is blocking the pore; this occurs after channels have opened and remain in a specific voltage region.

Refractory period

The period of time during which voltage-gated sodium channels are in the inactivated state and require repolarization of the membrane potential ($V_m$) to recover.

P-loops

Extracellular loops linking the $S5$ and $S6$ pore-forming regions in each domain; they form the extracellular mouth of the pore and determine ion selectivity.

DEKA sequence

A sequence of four amino acids—Aspartic acid ($D$), Glutamic acid ($E$), Lysine ($K$), and Alanine ($A$)—located on the permeation loops that confer high sodium ion selectivity.

Tetrodotoxin (TTX)

A toxin first isolated from Puffer fish (Tetraodontidae) that targets Site 1 of the VGSC alpha subunit to block conduction.

IG loop (Immunoglobulin loop)

A structure found in the extracellular domain of beta subunits that is responsible for modulating biophysical properties and acting as a cell adhesion molecule.

$\beta1B$ subunit

A soluble, secreted isoform of the beta subunit that lacks a transmembrane domain but can still associate with alpha subunits and modulate their properties.

Cell adhesion molecules

A role performed by VGSC beta subunits, independent of alpha subunits, which is important for axonal fasciculation and pathfinding during neurite extension.