Hullin R, Singer-Lahat D, Freichel M, Biel M, Dascal N, Hofmann F, Flockerzi V
Institut für Pharmakologie und Toxikologie, Technische Universität München, FRG.
EMBO J. 1992 Mar;11(3):885-90. doi: 10.1002/j.1460-2075.1992.tb05126.x.
Complementary DNAs encoding three novel and distinct beta subunits (CaB2a, CaB2b and CaB3) of the high voltage activated (L-type) calcium channel have been isolated from rabbit heart. Their deduced amino acid sequence is homologous to the beta subunit originally cloned from skeletal muscle (CaB1). CaB2a and CaB2b are splicing products of a common primary transcript (CaB2). Northern analysis and specific amplification of CaB2 and CaB3 specific cDNAs by polymerase chain reactions showed that CaB2 is predominantly expressed in heart, aorta and brain, whereas CaB3 is most abundant in brain but also present in aorta, trachea, lung, heart and skeletal muscle. A partial DNA sequence complementary to a third variant of the CaB2 gene, subtype CaB2c, has also been cloned from rabbit brain. Coexpression of CaB2a, CaB2b and CaB3 with alpha 1heart enhances not only the expression in the oocyte of the channel directed by the cardiac alpha 1 subunit alone, but also effects its macroscopic characteristics such as drug sensitivity and kinetics. These results together with the known alpha 1 subunit heterogeneity, suggest that different types of calcium currents may depend on channel subunit composition.
已从兔心脏中分离出编码高压激活(L型)钙通道三种新型且不同的β亚基(CaB2a、CaB2b和CaB3)的互补DNA。它们推导的氨基酸序列与最初从骨骼肌克隆的β亚基(CaB1)同源。CaB2a和CaB2b是共同初级转录本(CaB2)的剪接产物。通过聚合酶链反应对CaB2和CaB3特异性cDNA进行Northern分析和特异性扩增表明,CaB2主要在心脏、主动脉和大脑中表达,而CaB3在大脑中最丰富,但也存在于主动脉、气管、肺、心脏和骨骼肌中。还从兔脑中克隆了与CaB2基因的第三个变体CaB2c互补的部分DNA序列。CaB2a、CaB2b和CaB3与α1心脏亚基共表达不仅增强了仅由心脏α1亚基指导的通道在卵母细胞中的表达,还影响其宏观特性,如药物敏感性和动力学。这些结果与已知的α1亚基异质性一起表明,不同类型的钙电流可能取决于通道亚基组成。