Voltage-gated sodium channel (inactivated state) (NaV (inactivated state))

Voltage-gated sodium channels (VGSCs) are critical transmembrane proteins responsible for the rapid upstroke of action potentials in excitable tissues such as the brain, heart, and skeletal muscle. These channels transition through distinct functional states: resting (closed), open (conducting), and inactivated (non-conducting). The inactivated state is a refractory period that follows channel opening, mediated by an intracellular loop that plugs the pore to prevent further sodium influx. Pharmacologically, the inactivated state is a major target for state-dependent drugs like local anesthetics, anticonvulsants, and class I antiarrhythmics. These agents bind preferentially to the inactivated conformation, effectively stabilizing it and reducing the availability of channels for subsequent activation. This mechanism allows for the selective inhibition of high-frequency firing or persistently depolarized cells, which is essential for treating pathological conditions like epilepsy, chronic pain, and cardiac arrhythmias while minimizing effects on normal tissue. Understanding the transition between fast and slow inactivation states is also vital for developing next-generation drugs with improved safety profiles.

Other names

Sodium channel inactivated stateNaV channel inactivated stateFast-inactivated stateSlow-inactivated stateVGSC inactivated state

State-dependent inhibition where drugs bind with higher affinity to the inactivated conformation of the channel, leading to use-dependent block and stabilization of the non-conducting state.