Zong S, Zhou J, Tanabe T
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06536-0812.
Biochem Biophys Res Commun. 1994 Jun 30;201(3):1117-23. doi: 10.1006/bbrc.1994.1821.
We investigated the nature and structural requirements for Ca(2+)-dependent inactivation of cardiac L-type Ca2+ channel. Investigation of subunit requirements indicates that the interaction of alpha 1 subunit with ancillary subunits, especially beta subunit, is important for this property. Replacement of the putative cytoplasmic regions of the cardiac alpha 1 subunit with skeletal muscle counterparts eliminates Ca(2+)-dependent inactivation, indicating that the site regulated by Ca2+ resides in the cytoplasmic region of the alpha 1 subunit. Deletion of the carboxy-terminal region of the cardiac alpha 1 subunit does not eliminate this property, suggesting that the modulation by protein kinase A may not be involved in this mechanism. Single amino acid substitution that strongly reduces Ca2+ selectivity of Ca2+ channels also eliminates Ca(2+)-dependent inactivation, suggesting the close link between the ion selectivity and Ca(2+)-dependent inactivation.
我们研究了心脏L型钙通道钙依赖性失活的性质和结构要求。对亚基需求的研究表明，α1亚基与辅助亚基（尤其是β亚基）的相互作用对该特性很重要。用骨骼肌对应区域替换心脏α1亚基的假定胞质区域可消除钙依赖性失活，表明受Ca2+调节的位点位于α1亚基的胞质区域。删除心脏α1亚基的羧基末端区域并不会消除该特性，这表明蛋白激酶A的调节可能不参与此机制。强烈降低钙通道钙选择性的单氨基酸取代也消除了钙依赖性失活，表明离子选择性与钙依赖性失活之间存在密切联系。
