SCN5A and Sinoatrial Node Pacemaker Function

The SCN5A gene encodes specific voltage-dependent Na+ channels abundant in cardiac muscle that open and close at specific stages of cardiac activity in response to voltage change, thereby controlling the magnitude and timecourse of voltage-dependent Na+ currents (iNa) in cardiac muscle cells. Although iNa has been recorded from sinoatrial (SA) node pacemaker cells, its precise role in SA node pacemaker function remains uncertain. This review summarizes recent findings bearing upon: (i) Sinus node dysfunction resulting from genetic mutations in SCN5A; (ii) Sinus node function in the murine cardiac model with targeted disruptions of the SCN5A gene; (iii) Experimental and computational evaluations of the functional roles of iNa in SA node pacemaker function. Taken together, these new observations suggest strong correlations between SCN5A-encoded Na+ channel and SA node pacemaker function.