Varadi G, Mikala G, Lory P, Varadi M, Drouet B, Pinçon-Raymond M, Schwartz A
Institute of Molecular Pharmacology and Biophysics, University of Cincinnati, OH 45267-0828, USA.
FEBS Lett. 1995 Jul 24;368(3):405-10. doi: 10.1016/0014-5793(95)00697-8.
The expression of subunit genes of the Ca2+ channel complex was studied in differentiating, immortalized mouse mdg cells. These cells expressed alpha 1 and alpha 2/delta transcripts of the skeletal muscle Ca2+ channel genes, a cardiac Ca2+ channel alpha 1 subunit gene and several known transcript variants of skeletal, cardiac and brain beta genes. The mdg mutation is retained in the 129DA3 cell line and occurs exclusively at nucleotide position 4010 in the skeletal alpha 1 transcript in which a cytosine residue is deleted. In early stages of differentiation and fusion, Ba2+ currents were detected in dysgenic myotubes the same as the cardiac L-type Ca2+ channel. These data provide specific structural evidence [Chaudhari, N. (1992) J. Biol. Chem. 267, 25636-25639] for the major genetic defect in mouse muscular dysgenesis and show a change in the expression levels of alpha 1S and alpha 1C. The upregulation of the expression of alpha 1C results in functional Ca2+ channel activity, however, presumably not sufficient for excitation-contraction coupling.
在永生化的分化小鼠mdg细胞中研究了Ca2+通道复合体亚基基因的表达。这些细胞表达骨骼肌Ca2+通道基因的α1和α2/δ转录本、心脏Ca2+通道α1亚基基因以及骨骼肌、心脏和脑β基因的几种已知转录变体。mdg突变保留在129DA3细胞系中，且仅发生在骨骼肌α1转录本的第4010位核苷酸处，该位置的一个胞嘧啶残基缺失。在分化和融合的早期阶段，在发育不全的肌管中检测到Ba2+电流，与心脏L型Ca2+通道相同。这些数据为小鼠肌肉发育不全的主要遗传缺陷提供了具体的结构证据[Chaudhari, N. (1992) J. Biol. Chem. 267, 25636 - 25639]，并显示了α1S和α1C表达水平的变化。α1C表达的上调导致功能性Ca2+通道活性，然而，这可能不足以实现兴奋 - 收缩偶联。
