Practice question

Gating mechanisms classify ion channels by physiological stimulus that controls transition from closed to open conformation. Voltage-gated channels possess specialized voltage-sensing domains where transmembrane segment S4 contains repeating positively charged arginine or lysine residues every third position, acting as sliding helix that moves outward upon membrane depolarization, pulling on S4-S5 linker and opening activation gate at intracellular bundle crossing. Neuronal voltage-gated sodium channels, Nav1.1 to Nav1.9 encoded by SCN genes, contain four homologous domains each with six helices, activating within microseconds at threshold around minus fifty millivolts to initiate rapid upstroke of action potential then fast inactivating via intracellular IFM motif blocking pore, allowing unidirectional propagation. Potassium voltage-gated channels Kv repolarize membrane. This voltage dependence enables regenerative electrical signaling along axons and muscle excitation-contraction coupling. In contrast aquaporins are constitutively open tetrameric water channels with NPA motifs lacking voltage sensor, nicotinic acetylcholine receptors are ligand-gated cation channels activated by acetylcholine binding to extracellular domain, and GLUT4 is facilitative glucose carrier not ion channel. Voltage gating confers excitability, targeted by local anesthetics, antiepileptics and toxins like tetrodotoxin.