Nav1.5 (D9J7S) Rabbit Monoclonal Antibody #14421

Voltage gated sodium channels are composed of a large alpha subunit and auxiliary beta subunits. The alpha subunit has 4 homologous domains, with each domain containing 6 transmembrane segments. These segments function as the voltage sensor and sodium permeable pore. Upon change of membrane potential, the sodium channel is activated, which allows sodium ions to flow through (1,2). When associated with beta subunits or other accessory proteins, the alpha subunit is regulated at the level of cell surface expression, kinetics, and voltage dependence (3,4).

There are 9 mammalian alpha subunits, named Nav1.1-Nav1.9 (5). These alpha subunits differ in tissue specificity and biophysical functions (6,7). Seven of these subunits are essential for the initiation and propagation of action potentials in the central and peripheral nervous system while Nav1.4 and Nav1.5 are mainly expressed in skeletal muscle and cardiac muscle (8,9). Mutations in these alpha channel subunits have been identified in patients with epilepsy, seizure, ataxia, sensitivity to pain, and cardiomyopathy (reviewed in 10).
Nav1.5 is a type V alpha subunit. It is expressed primarily in cardiac muscle and is accountable for the initiation and propagation of the cardiac action potentials (11). Mutations in the SCN5A gene encoding Nav1.5 have been associated with arrhythmic cardiac diseases such as Brugada syndrome, long QT syndrome 3, and Progressive familial heart block 1A (PFHB1A) (12-15). Nav1.5 is also expressed in jejunal circular smooth muscle (HJCSM) cells. Research studies identified loss of function of Nav1.5 in 2% of patients with irritable bowel syndrome (9,16). Nav1.5 has multiple splice variants, several of which are expressed in the brain (17-18).