Varadi G, Mori Y, Mikala G, Schwartz A
Institute of Molecular Pharmacology and Biophysics, University of Cincinnati, College of Medicine, OH 45267-0828, USA.
Trends Pharmacol Sci. 1995 Feb;16(2):43-9. doi: 10.1016/s0165-6147(00)88977-4.
Molecular cloning has revealed the existence of six high-voltage activated Ca2+ channel types. Expression studies have shown that basic high-voltage activated channel function, which is typical for the L-(skeletal muscle, cardiac muscle and neuroendocrine tissue), N-, P-, Q- and R-type channels is carried by the corresponding alpha 1 subunits. Auxiliary subunits, such as alpha 2/delta and beta, modulate the kinetics of activation, inactivation, current density and drug binding, thereby creating considerable potential for multiple Ca2+ channel functions. Glutamic acid residues in the pore (P) loops are molecular components that impart high selectivity for Ca+. Binding or pharmacologically active sites for Ca2+ channel drugs have been localized on various segments of the alpha 1 subunit in close proximity to the pore lining. In this article, Gyula Varadi and colleagues review the roles of the different subunits in Ca2+ channel function and suggest that Ca2+ channel drugs act by blocking or, in some cases, activating channel function via binding directly or indirectly to the pore structure of the channel.
分子克隆技术已揭示出六种高电压激活的钙离子通道类型。表达研究表明，L型（骨骼肌、心肌和神经内分泌组织）、N型、P型、Q型和R型通道典型的基本高电压激活通道功能由相应的α1亚基承担。辅助亚基，如α2/δ和β亚基，可调节激活、失活的动力学过程、电流密度及药物结合，从而为多种钙离子通道功能创造了相当大的潜力。孔道（P）环中的谷氨酸残基是赋予对钙离子高选择性的分子成分。钙离子通道药物的结合位点或药理活性位点已定位在α1亚基靠近孔道衬里的各个片段上。在本文中，久洛·瓦拉迪及其同事回顾了不同亚基在钙离子通道功能中的作用，并提出钙离子通道药物通过直接或间接结合通道的孔道结构来阻断通道功能，在某些情况下则是激活通道功能。
