Characterization of Sodium Channel α- and β-Subunits in Rat and Mouse Cardiac Myocytes

Abstract

Background —Sodium channels isolated from mammalian brain are composed of α-, β 1 -, and β 2 -subunits. The composition of sodium channels in cardiac muscle, however, has not been defined, and disagreement exists over which β-subunits are expressed in the myocytes. Some investigators have demonstrated β 1 expression in heart. Others have not detected any auxiliary subunits. On the basis of Northern blot analysis of total RNA, β 2 expression has been thought to be exclusive to neurons and absent from cardiac muscle. Methods and Results —The goal of this study was to define the subunit composition of cardiac sodium channels in myocytes. We show that cardiac sodium channels are composed of α-, β 1 -, and β 2 -subunits. Nav1.5 and Nav1.1 are expressed in myocytes and are associated with β 1 - and β 2 -subunits. Immunocytochemical localization of Nav1.1, β 1 , and β 2 in adult heart sections showed that these subunits are expressed at the Z lines, as shown previously for Nav1.5. Coexpression of Nav1.5 with β 2 in transfected cells resulted in no detectable changes in sodium current. Conclusions —Cardiac sodium channels are composed of α- (Nav1.1 or Nav1.5), β 1 -, and β 2 -subunits. Although β 1 -subunits modulate cardiac sodium channel current, β 2 -subunit function in heart may be limited to cell adhesion.