Modulation of cardiac Na+ channel expression in Xenopus oocytes by β1 subunits

Abstract

Voltage-gated Na+ channels consist of a large α subunit of 260 kDa associated with β1 and/or β2 subunits of 36 and 33 kDa, respectively. α subunits of rat cardiac Na+ channels (rH1) are functional when expressed alone in Xenopus oocytes or mammalian cells. β1 subunits are present in the heart, and localization of β1 subunit mRNA by in situ hybridization shows expression in the perinuclear cytoplasm of cardiac myocytes. Coexpression of β1 subunits with rH1 α subunits in Xenopus oocytes increases Na+ currents up to 6-fold in a concentration-dependent manner. However, no effects of β1 subunit coexpression on the kinetics or voltage dependence of the rH1 Na+ current were detected. Increased expression of Na+ currents is not observed when an equivalent mRNA encoding a nonfunctional mutant β1 subunit is coexpressed. Our results show that β1 subunits are expressed in cardiac muscle cells and that they interact with α subunits to increase the expression of cardiac Na+ channels in Xenopus oocytes, suggesting that β1 subunits are important determinants of the level of excitability of cardiac myocytes in vivo.