Physiology of Nav1.7

Physiology of Na_v1.7

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 Na_v1.7 channel produces a rapidly activating and inactivating current that is sensitive to submicromolar levels of tetrodotoxin. This is in contrast with Na_v1.8, which is also present within DRG neurons but is fairly resistant to tetrodotoxin. Na_v1.7 appears to be important in early phases of neuronal electrogenesis. Na_v1.7 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, Na_v1.7 acts as a “threshold channel” that amplifies small, subtle depolarizations such as generator potentials, thereby bringing neurons to voltages that stimulate Na_v1.8, 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, Na_v1.7 is poised as a molecular gatekeeper of pain detection at peripheral nociceptors.