Friday, August 24, 2012

Physiology of Nav1.7

Physiology of Nav1.7
In sensory neurons, multiple voltage-dependent sodium currents can be differentiated by their gating kinetics and voltage dependence and can also be defined by their sensitivity to the voltage gated sodium-channel blocker tetrodotoxin. The Nav1.7 channel produces a rapidly activating and inactivating current that is sensitive to submicromolar levels of tetrodotoxin. This is in contrast with Nav1.8, which is also present within DRG neurons but is fairly resistant to tetrodotoxin. Nav1.7 appears to be important in early phases of neuronal electrogenesis. Nav1.7 is characterized by slow transition of the channel into an inactive state when it is depolarized, even to a minor degree, a property that allows these channels to remain available for activation with small or slowly developing depolarizations, usually mimicked by electrophysiologists as ramp-like stimuli. Thus, Nav1.7 acts as a “threshold channel” that amplifies small, subtle depolarizations such as generator potentials, thereby bringing neurons to voltages that stimulate Nav1.8, which has a more depolarized activation threshold and which produces most of the transmembrane current responsible for the depolarizing phase of action potentials. In this regard, Nav1.7 is poised as a molecular gatekeeper of pain detection at peripheral nociceptors.

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