title: Physiology and Pathophysiology of Sodium Channel Inactivation.
abstract: Voltage-gated sodium channels are present in different tissues within the human body, predominantly nerve, muscle, and heart. The sodium channel is composed of four similar domains, each containing six transmembrane segments. Each domain can be functionally organized into a voltage-sensing region and a pore region. The sodium channel may exist in resting, activated, fast inactivated, or slow inactivated states. Upon depolarization, when the channel opens, the fast inactivation gate is in its open state. Within the time frame of milliseconds, this gate closes and blocks the channel pore from conducting any more sodium ions. Repetitive or continuous stimulations of sodium channels result in a rate-dependent decrease of sodium current. This process may continue until the channel fully shuts down. This collapse is known as slow inactivation. This chapter reviews what is known to date regarding, sodium channel inactivation with a focus on various mutations within each NaV subtype and with clinical implications.
authors: Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada.
authors: M-R
authors: MR
authors: Ghovanloo
authors: Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada.
authors: K
authors: K
authors: Aimar
authors: Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada.
authors: R
authors: R
authors: Ghadiry-Tavi
authors: Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada.
authors: A
authors: A
authors: Yu
authors: Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada.
authors: P C
authors: PC
authors: Ruben
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D009498:Neurotoxins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism; D061567:Voltage-Gated Sodium Channel Blockers / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry / Q000378:metabolism*
chemical_list: D009498:Neurotoxins; D020033:Protein Isoforms; D021122:Protein Subunits; D061567:Voltage-Gated Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels
keywords: Arrhythmia; Channelopathies; Epilepsy; Fast inactivation; Gating; Kinetics; Slow inactivation; Toxins; Voltage dependence