Molecular cloning of calcium channel α2δ-subunits from rat atria and the differential regulation of their expression by IGF-1
Molecular cloning of calcium channel α2δ-subunits from rat atria and the differential regulation of their expression by IGF-1
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DOI：
10.1016/s0022-2828(02)00313-9
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发表时间：
2003-02-01
影响因子：
5
通讯作者：
Best, PM
中科院分区：
文献类型：
--
作者：
Chu, PJ;Best, PM
钙通道是由成孔（α（1））和辅助（α（2）、δ、β、γ）亚基组成的多聚体蛋白。当与一些但不是全部α（1）亚基共表达时，辅助α（2）δ亚基调节钙电流密度和激活/失活动力学。在此，我们报告了大鼠心房、心房肌细胞和心室中三种α（2）δ-亚基cDNA的差异表达，并证明IGF-1选择性地增加了心房中α（2）δ-3 mRNA的表达。在大鼠心室中检测到编码α（2）δ-1-和α（2）δ-2-亚基的mRNA，但未检测到编码α（2）δ-3-亚基的mRNA，而在心房组织中发现了所有三种转录物。对大鼠α（2）δ-1cDNA序列的分析表明，心房表达该基因的α（2）δ-1e选择性剪接同种型。测定了大鼠心房α（2）δ-2-亚基和α（2）δ-3-亚基的完整cDNA序列，发现它们与小鼠心房的对应物分别具有96%和95%的同一性。用IGF-1处理急性培养的心房肌细胞，可引起α（2）δ-3 mRNA量的显著增加，但α（2）δ-1或α（2）δ-2 mRNA量无显著增加。L型和T型钙电流都是从心脏组织中记录的，尽管它们的表达是区域特异性的，并且随着年龄和生理状态而变化。α（2）δ亚基基因表达的差异调节可能有助于哺乳动物心脏钙电流表达的改变。(C)2003爱思唯尔科技有限公司版权所有。
Calcium channels are multimeric proteins consisting of pore-forming (alpha(1)) and auxiliary (alpha(2)delta, beta, gamma) subunits. The auxiliary alpha(2)delta-subunit regulates calcium current density and activation/inactivation kinetics when co-expressed with some, but not all, alpha(1)-subunits. Here we report the differential expression of three alpha(2)delta-subunit cDNAs in rat atria, atrial myocytes and ventricle, and demonstrate that IGF-1 selectively increases the expression of the alpha(2)delta-3 mRNA in the atria. mRNA encoding the alpha(2)delta-1- and alpha(2)delta-2-subunits, but not the alpha(2)delta-3-subunit, is detected in the rat ventricle whereas all three transcripts are found in atrial tissue. Analysis of the rat alpha(2)delta-1 cDNA sequence indicates that the atria express the alpha(2)delta-1e alternatively spliced isoform of this gene. The complete cDNA sequences of the alpha(2)delta-2- and a(2)delta-3-subunits from rat atria were determined and found to share 96% and 95% identity, respectively, with their counterparts in mouse. Treatment of acutely cultured atrial myocytes with IGF-1 caused a significant increase of the amount of alpha(2)delta-3, but not alpha(2)delta-1 or alpha(2)delta-2, mRNA. Both L-type and T-type calcium currents are recorded from cardiac tissue although their expression is regionally specific and changes with age and physiological state. Differential regulation of the expression of alpha(2)delta-subunit genes is likely to contribute to alterations in the expression of calcium current in the mammalian heart. (C) 2003 Elsevier Science Ltd. All rights reserved.