Sodium channel protein type 4 subunit alpha (NaV1.4) and Sodium channel protein type 5 subunit alpha (NaV1.5) (NaV1.4/NaV1.5)

Voltage-gated sodium channels (VGSCs) in muscle tissue, primarily represented by the NaV1.4 and NaV1.5 isoforms, are essential transmembrane proteins that initiate and propagate action potentials. NaV1.4 (encoded by SCN4A) is specifically expressed in skeletal muscle, where its activation triggers the calcium release necessary for muscle contraction (UniProt: P35499). NaV1.5 (encoded by SCN5A) is the predominant isoform in the heart, responsible for the rapid upstroke of the cardiac action potential and the maintenance of normal conduction velocity (UniProt: Q14524). Mutations in these channels lead to a variety of channelopathies, including skeletal muscle disorders like myotonia and periodic paralysis, as well as life-threatening cardiac conditions such as Brugada syndrome and Long QT syndrome type 3 (StatPearls: Sodium Channelopathies). Pharmacological agents targeting these channels, such as mexiletine and lidocaine, are used to manage these conditions by blocking the sodium pore or altering gating kinetics to reduce pathological hyperexcitability (PubChem: Mexiletine; PubChem: Lidocaine). However, therapeutic use is often limited by the need for isoform selectivity to avoid adverse effects in the central nervous system or unintended cardiac/skeletal muscle interference (PubMed: 29453117).

Other names

SCN4ASCN5ASkM1h1Muscle sodium channelVoltage-gated sodium channel type IVVoltage-gated sodium channel type V

Inhibition of sodium ion conductance by binding to the S6 segments of the alpha-subunit, typically stabilizing the inactivated state or blocking the open pore to reduce membrane excitability (PubMed: 29453117).