MODULATION OF CARDIAC NA-1 SUBUNITS( CHANNEL EXPRESSION IN XENOPUS OOCYTES BY BETA)

Voltage-gated Na+ channels consist of a large alpha subunit of 260 kDa associated with beta 1 and/or beta 2 subunits of 36 and 33 kDa, respe ctively. alpha subunits of rat cardiac Na+ channels (rH1) are function al when expressed alone in Xenopus oocytes or mammalian cells. beta 1 subunits are present in the heart, and localization of beta 1 subunit mRNA by in situ hybridization shows expression in the perinuclear cyto plasm of cardiac myocytes. Coexpression of beta 1 subunits with rH1 al pha subunits in Xenopus oocytes increases Na+ currents up to 6-fold in a concentration dependent manner. However, no effects of beta 1 subun it coexpression on the kinetics or voltage dependence of the rH1 Na+ c urrent were detected. Increased expression of Na+ currents is not obse rved when an equivalent mRNA encoding a nonfunctional mutant beta 1 su bunit is coexpressed. Our results show that beta 1 subunits are expres sed in cardiac muscle cells and that they interact with alpha subunits to increase the expression of cardiac Na+ channels in Xenopus oocytes , suggesting that beta 1 subunits are important determinants of the le vel of excitability of cardiac myocytes in vivo.