Voltage-gated sodium channel-associated proteins and alternative mechanisms of inactivation and block |
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Authors: | Email author" target="_blank">Mitchell?GoldfarbEmail author |
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Institution: | (1) Department of Biological Sciences, Hunter College of City University, New York, NY 10065, USA |
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Abstract: | Voltage-gated sodium channels mediate inward current of action potentials upon membrane depolarization of excitable cells.
The initial transient sodium current is restricted to milliseconds through three distinct channel-inactivating and blocking
mechanisms. All pore-forming alpha subunits of sodium channels possess structural elements mediating fast inactivation upon
depolarization and recovery within milliseconds upon membrane repolarization. Accessory subunits modulate fast inactivation
dynamics, but these proteins can also limit current by contributing distinct inactivation and blocking particles. A-type isoforms
of fibroblast growth factor homologous factors (FHFs) bear a particle that induces long-term channel inactivation, while sodium
channel subunit Navβ4 employs a blocking particle that rapidly dissociates upon membrane repolarization to generate resurgent
current. Despite their different physiological functions, the FHF and Navβ4 particles have similarity in amino acid composition
and mechanisms for docking within sodium channels. The three competing channel-inactivating and blocking processes functionally
interact to regulate a neuron’s intrinsic excitability. |
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Keywords: | |
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