Obermair Gerald J, Tuluc Petronel, Flucher Bernhard E
Division of Physiology, Department of Physiology and Medical Physics, Medical University Innsbruck, Fritz-Pregl-Str. 3, 6020 Innsbruck, Austria.
Curr Opin Pharmacol. 2008 Jun;8(3):311-8. doi: 10.1016/j.coph.2008.01.008. Epub 2008 Mar 7.
Voltage-gated Ca(2+) channels are multi-subunit complexes involved in many key functions of excitable cells. A multitude of studies in heterologous cells demonstrated that coexpression of the pore-forming alpha(1) subunits with auxiliary alpha(2)delta and beta subunits promotes membrane expression and modulates the biophysical channel properties. New null-mutant animal models and shRNA based knockdown experiments in skeletal muscle cells for the first time demonstrated the physiological roles and possible pathological effects of the alpha(2)delta-1 and beta(1a) subunits in a differentiated excitable cell. The alpha(2)delta-1 subunit is the determinant of the typical current properties of skeletal and cardiac muscle Ca(2+) channels. The beta(1a) subunit links the skeletal muscle Ca(2+) channel to the Ca(2+) release channel in the sarcoplasmic reticulum. Whether these specific functions in muscle indicate similar roles of alpha(2)delta and beta subunits as functional modulator and structural organizer, respectively, in neurons is being discussed.
电压门控性Ca(2+)通道是参与可兴奋细胞许多关键功能的多亚基复合物。在异源细胞中进行的大量研究表明，形成孔道的α(1)亚基与辅助性α(2)δ和β亚基共表达可促进膜表达并调节通道的生物物理特性。新的基因敲除动物模型以及基于短发夹RNA（shRNA）的骨骼肌细胞敲低实验首次证明了α(2)δ-1和β(1a)亚基在分化的可兴奋细胞中的生理作用及可能的病理效应。α(2)δ-1亚基是骨骼肌和心肌Ca(2+)通道典型电流特性的决定因素。β(1a)亚基将骨骼肌Ca(2+)通道与肌浆网中的Ca(2+)释放通道相连。目前正在讨论这些在肌肉中的特定功能是否分别表明α(2)δ和β亚基在神经元中作为功能调节剂和结构组织者具有类似作用。
