β1亚基与非洲爪蟾卵母细胞中表达的人心肌（hH1）和大鼠骨骼肌（μ1）钠通道α亚基的功能关联。
Functional association of the beta 1 subunit with human cardiac (hH1) and rat skeletal muscle (mu 1) sodium channel alpha subunits expressed in Xenopus oocytes.
作者信息
Nuss H B, Chiamvimonvat N, Pérez-García M T, Tomaselli G F, Marbán E
机构信息
Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
出版信息
J Gen Physiol. 1995 Dec;106(6):1171-91. doi: 10.1085/jgp.106.6.1171.
Native cardiac and skeletal muscle Na channels are complexes of alpha and beta 1 subunits. While structural correlates for activation, inactivation, and permeation have been identified in the alpha subunit and the expression of alpha alone produces functional channels, beta 1-deficient rat skeletal muscle (mu 1) and brain Na channels expressed in Xenopus oocytes do not gate normally. In contrast, the requirement of a beta 1 subunit for normal function of Na channels cloned from rat heart or human heart (hH1) has been disputed. Coinjection of rat brain beta 1 subunit cRNA with hH1 (or mu 1) alpha subunit cRNA into oocytes increased peak Na currents recorded 2 d after injection by 240% (225%) without altering the voltage dependence of activation. In mu 1 channels, steady state inactivation was shifted to more negative potentials (by 6 mV, p < 0.01), but the shift of 2 mV was not significant for hH1 channels. Nevertheless, coexpression with beta 1 subunit speeded the decay of macroscopic current of both isoforms. Ensemble average hH1 currents from cell-attached patches revealed that coexpression of beta 1 increases the rate of inactivation (quantified by time to 75% decay of current; p < 0.01 at -30, -40, and -50 mV). Use-dependent decay of hH1 Na current during repeated pulsing to -20 mV (1 s, 0.5 Hz) after a long rest was reduced to 16 +/- 2% of the first pulse current in oocytes coexpressing alpha and beta 1 subunits compared to 35 +/- 8% use-dependent decay for oocytes expressing the alpha subunit alone. Recovery from inactivation of mu 1 and hH1 Na currents after 1-s pulses to -20 mV is multiexponential with three time constants; coexpression of beta 1 subunit decreased all three recovery time constants. We conclude that the beta 1 subunit importantly influences the function of Na channels produced by coexpression with either the hH1 or mu 1 alpha subunits.
天然心肌和骨骼肌钠通道是α和β1亚基的复合物。虽然已在α亚基中确定了激活、失活和通透的结构关联，且单独表达α就能产生功能性通道，但β1缺陷型大鼠骨骼肌（μ1）和在非洲爪蟾卵母细胞中表达的脑钠通道不能正常门控。相比之下，对于从大鼠心脏或人类心脏克隆的钠通道（hH1）正常功能是否需要β1亚基一直存在争议。将大鼠脑β1亚基cRNA与hH1（或μ1）α亚基cRNA共注射到卵母细胞中，可使注射后2天记录到的钠电流峰值增加240%（225%），而不改变激活的电压依赖性。在μ1通道中，稳态失活向更负的电位偏移（6 mV，p<0.01），但对于hH1通道，2 mV的偏移不显著。然而，与β1亚基共表达加快了两种亚型宏观电流的衰减。来自细胞贴附膜片的整体平均hH1电流显示，β1的共表达增加了失活速率（通过电流衰减至75%的时间量化；在-30、-40和-50 mV时p<0.01）。在长时间休息后，将hH1钠电流重复脉冲至-20 mV（1 s，0.5 Hz）时的使用依赖性衰减，在共表达α和β1亚基的卵母细胞中降至第一个脉冲电流的16±2%，而单独表达α亚基的卵母细胞的使用依赖性衰减为35±8%。在向-20 mV施加1秒脉冲后，μ1和hH1钠电流从失活状态恢复是具有三个时间常数的多指数过程；β1亚基的共表达降低了所有三个恢复时间常数。我们得出结论，β1亚基与hH1或μ1α亚基共表达时，对所产生的钠通道功能有重要影响。
Zotero 插件