Heterologous regulation of the cardiac Ca2+ channel alpha 1 subunit by skeletal muscle beta and gamma subunits. Implications for the structure of cardiac L-type Ca2+ channels.
Heterologous regulation of the cardiac Ca2+ channel alpha 1 subunit by skeletal muscle beta and gamma subunits. Implications for the structure of cardiac L-type Ca2+ channels.
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DOI：
10.1016/s0021-9258(18)54728-1
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发表时间：
1991-11
期刊：
影响因子：
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通讯作者：
X. Wei;E. Perez-Reyes;A. E. Lacerda;G. Schuster;A. Brown;L. Birnbaumer
中科院分区：
文献类型：
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作者：
X. Wei;E. Perez-Reyes;A. E. Lacerda;G. Schuster;A. Brown;L. Birnbaumer
骨骼肌的高阈值 L 型 Ca2+ 通道被认为由 alpha 1、alpha 2 delta、beta 和 gamma 亚基的复合体组成。骨骼肌和心肌中克隆的 α1 亚基的表达已确定该蛋白质是二氢吡啶敏感的离子传导亚基。然而，在小鼠L细胞中单独表达的骨骼肌α1的动力学异常缓慢，并且通过与骨骼肌β亚基共表达而加速至正常范围内。心肌α 1 的动力学也减慢，但程度较小，并且不因与骨骼肌α 2 共表达而改变。我们在此表明，非洲爪蟾卵母细胞中骨骼肌β亚基与心脏α 1 亚基的共表达产生：1）峰值电压敏感电流的增加，2）峰值电流-电压关系向更超极化电位的转变，以及3）速率的增加的激活。骨骼肌γ亚基的共表达对α1引起的电流没有显着影响。然而，当γ与β和α1共表达时，峰值电流和在更负电位下的激活速率均增加。这些结果表明，异源骨骼肌β和γ亚基可以调节心脏α1的生物物理特性，而不是简单地放大α1的表达。
High threshold L-type Ca2+ channels of skeletal muscle are thought to consist of a complex of alpha 1, alpha 2 delta, beta, and gamma subunits. Expression of the cloned alpha 1 subunit from skeletal and cardiac muscle has established that this protein is the dihydropyridine-sensitive ion-conducting subunit. However, the kinetics of the skeletal muscle alpha 1 alone expressed in mouse L-cells were abnormally slow and were accelerated to within the normal range by coexpression with the skeletal muscle beta subunit. The kinetics of cardiac muscle alpha 1 were also slowed but to a lesser extent and were not altered by coexpression with skeletal muscle alpha 2. We show here that coexpression of the skeletal muscle beta subunit with the cardiac alpha 1 subunit in Xenopus laevis oocytes produced: 1) an increase in the peak voltage-sensitive current, 2) a shift of the peak current-voltage relationship to more hyperpolarized potentials, and 3) an increase in the rate of activation. Coexpression of the skeletal muscle gamma subunit did not have a significant effect on currents elicited by alpha 1. However, when gamma was coexpressed with beta and alpha 1, both peak currents and rates of activation at more negative potentials were increased. These results indicate that rather than simply amplifying expression of alpha 1, heterologous skeletal muscle beta and gamma subunits can modulate the biophysical properties of cardiac alpha 1.