Qu Y, Isom L L, Westenbroek R E, Rogers J C, Tanada T N, McCormick K A, Scheuer T, Catterall W A
Department of Pharmacology, University of Washington, Seattle 98195-7280, USA.
J Biol Chem. 1995 Oct 27;270(43):25696-701. doi: 10.1074/jbc.270.43.25696.
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, respectively. alpha subunits of rat cardiac Na+ channels (rH1) are functional 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 cytoplasm of cardiac myocytes. Coexpression of beta 1 subunits with rH1 alpha subunits in Xenopus oocytes increases Na+ currents up to 6-fold in a concentration-dependent manner. However, no effects of beta 1 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 beta 1 subunit is coexpressed. Our results show that beta 1 subunits are expressed 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 level of excitability of cardiac myocytes in vivo.
电压门控性钠离子通道由一个260 kDa的大α亚基与分别为36 kDa和33 kDa的β1和/或β2亚基相关联组成。大鼠心脏钠离子通道（rH1）的α亚基在非洲爪蟾卵母细胞或哺乳动物细胞中单独表达时具有功能。β1亚基存在于心脏中，通过原位杂交对β1亚基mRNA进行定位显示其在心肌细胞的核周细胞质中表达。在非洲爪蟾卵母细胞中，β1亚基与rH1α亚基共表达可使钠离子电流以浓度依赖性方式增加至6倍。然而，未检测到β1亚基共表达对rH1钠离子电流的动力学或电压依赖性有影响。当共表达编码无功能突变β1亚基的等量mRNA时，未观察到钠离子电流表达增加。我们的结果表明，β1亚基在心肌细胞中表达，并且它们与α亚基相互作用以增加非洲爪蟾卵母细胞中心脏钠离子通道的表达，这表明β1亚基是体内心肌细胞兴奋性水平的重要决定因素。
