Knudson C M, Chaudhari N, Sharp A H, Powell J A, Beam K G, Campbell K P
Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City 52242.
J Biol Chem. 1989 Jan 25;264(3):1345-8.
Muscular dysgenesis is a lethal mutation in mice that results in a complete absence of skeletal muscle contraction due to the failure of depolarization of the transverse tubular membrane to trigger calcium release from the sarcoplasmic reticulum. In order to determine whether the defect in muscular dysgenesis leads to a specific loss of one of the components of excitation-contraction coupling or to a generalized loss of all components of excitation-contraction coupling, we have analyzed skeletal muscle from control and dysgenic mice for the sarcoplasmic reticulum and transverse tubular proteins which are believe to function in excitation-contraction coupling. We report that the proteins involved in sarcoplasmic reticulum calcium transport, storage, and release [Ca2+ + Mg2+)-ATPase, calsequestrin, and calcium release channel) are present in dysgenic muscle. Also present in dysgenic muscle is the 175/150-kDa glycoprotein subunit (alpha 2) of the dihydropyridine receptor. However, the 170-kDa dihydropyridine binding subunit (alpha 1) of the dihydropyridine receptor is absent in dysgenic muscle. These results suggest that the specific absence of the alpha 1 subunit of the dihydropyridine receptor is responsible for the defects in muscular dysgenesis and that the alpha 1 subunit of the dihydropyridine receptor is essential for excitation-contraction coupling in skeletal muscle.
肌肉发育不全是小鼠中的一种致死性突变，由于横管膜去极化失败，无法触发肌浆网释放钙，导致骨骼肌完全无法收缩。为了确定肌肉发育不全的缺陷是导致兴奋-收缩偶联的某一成分特异性缺失还是导致兴奋-收缩偶联所有成分的普遍缺失，我们分析了对照小鼠和发育不全小鼠骨骼肌中的肌浆网和横管蛋白，这些蛋白被认为在兴奋-收缩偶联中发挥作用。我们报告，参与肌浆网钙转运、储存和释放的蛋白（[Ca2+ + Mg2+)-ATP酶、肌集钙蛋白和钙释放通道）在发育不全的肌肉中存在。发育不全的肌肉中还存在二氢吡啶受体的175/150-kDa糖蛋白亚基（α2）。然而，发育不全的肌肉中不存在二氢吡啶受体的170-kDa二氢吡啶结合亚基（α1）。这些结果表明，二氢吡啶受体α1亚基的特异性缺失是肌肉发育不全缺陷的原因，并且二氢吡啶受体α1亚基对骨骼肌的兴奋-收缩偶联至关重要。
