Sodium channel traffic on the cardiac microtubule highway.

Voltage-gated sodium channels are responsible for excitable cell action potential initiation. In cardiomyocytes, SCN5A-encoded Nav1.5 is the primary voltage-gated sodium channel a subunit, although other Nav channel a subunits may secondarily modulate specific INa properties. In addition to the pore-forming Nav1.5 a subunits, four accessory Nav b subunits (b1–b4) are expressed in the human heart. These b subunits have been hypothesized to affect anterograde membrane trafficking of Nav channel a subunits. The critical role of Nav1.5 for normal cardiac function is clearly demonstrated by cardiac defects in mice lacking Nav1.5 1 as well as by severe ventricular, atrial, and sinoatrial node arrhythmia phenotypes in patients harbouring gainor loss-of-function mutations in SCN5A or in Nav channel b subunits (b1–b4). 2