Sodium channel protein type 5 subunit alpha (SCN5A) (Nav1.5)

The Sodium channel protein type 5 subunit alpha, commonly known as Nav1.5, is a critical voltage-gated ion channel primarily expressed in the myocardium (UniProt P35498). It is responsible for the rapid influx of sodium ions during the initial phase of the cardiac action potential, which triggers the depolarization necessary for heart muscle contraction (PubMed: 25559375). Beyond its role in normal cardiac rhythm, Nav1.5 is a major focus in cardiovascular medicine due to its involvement in numerous inherited and acquired arrhythmias (NIH: GeneID 6331). Mutations in the SCN5A gene, which encodes this protein, are linked to life-threatening conditions such as Brugada syndrome and Long QT syndrome type 3 (StatPearls: NBK537033). Pharmacologically, Nav1.5 is the primary target for Class I antiarrhythmic drugs, which modulate its activity to manage rhythm disorders (PubChem: SCN5A). These drugs work by binding to the alpha subunit to inhibit the inward sodium current, thereby slowing conduction velocity or altering the refractory period. However, therapeutic targeting requires precision, as excessive blockade or unintended modulation can lead to dangerous proarrhythmic effects or impaired cardiac conduction (PubMed: 29433358). Recent research also explores Nav1.5 expression in non-cardiac tissues, including its potential role in cancer progression and metastasis (PubMed: 31611024).

Other names

SCN5ASodium channel protein type V subunit alphaHeart sodium channel alpha subunitSkM2HB1HB2CDCD2CMD1EICCDLQT3PFHB1SSS1Nav1.5

Class I antiarrhythmic drugs bind to and inhibit the Nav1.5 channel, reducing the peak inward sodium current (INa) to slow the rate of cardiac depolarization and conduction velocity (StatPearls: NBK537033). Some agents also target the late sodium current (INa,late) to reduce sodium-dependent calcium overload, which is beneficial in conditions like long QT syndrome type 3 and myocardial ischemia (PubMed: 29433358).