Fisher T E, Bourque C W
Department of Physiology, University of Saskatchewan, 107 Wiggins Road, Sask., S7N 5E5, Saskatoon, Canada.
Prog Biophys Mol Biol. 2001 Nov;77(3):269-303. doi: 10.1016/s0079-6107(01)00017-7.
By mediating the Ca(2+) influx that triggers exocytotic fusion, Ca(2+) channels play a central role in a wide range of secretory processes. Ca(2+) channels consist of a complex of protein subunits, including an alpha(1) subunit that constitutes the voltage-dependent Ca(2+)-selective membrane pore, and a group of auxiliary subunits, including beta, gamma, and alpha(2)-delta subunits, which modulate channel properties such as inactivation and channel targeting. Subtypes of Ca(2+) channels are constituted by different combinations of alpha(1) subunits (of which 10 have been identified) and auxiliary subunits, particularly beta (of which 4 have been identified). Activity-secretion coupling is determined not only by the biophysical properties of the channels involved, but also by the relationship between channels and the exocytotic apparatus, which may differ between fast and slow types of secretion. Colocalization of Ca(2+) channels at sites of fast release may depend on biochemical interactions between channels and exocytotic proteins. The aim of this article is to review recent work on Ca(2+) channel structure and function in exocytotic secretion. We discuss Ca(2+) channel involvement in selected types of secretion, including central neurotransmission, endocrine and neuroendocrine secretion, and transmission at graded potential synapses. Several different Ca(2+) channel subtypes are involved in these types of secretion, and their function is likely to involve a variety of relationships with the exocytotic apparatus. Elucidating the relationship between Ca(2+) channel structure and function is central to our understanding of the fundamental process of exocytotic secretion.
通过介导触发胞吐融合的钙离子内流,钙离子通道在广泛的分泌过程中发挥核心作用。钙离子通道由蛋白质亚基复合体组成,包括构成电压依赖性钙离子选择性膜孔的α1亚基,以及一组辅助亚基,包括β、γ和α2δ亚基,它们可调节通道特性,如失活和通道靶向。钙离子通道亚型由α1亚基(已鉴定出10种)和辅助亚基,特别是β亚基(已鉴定出4种)的不同组合构成。活性-分泌偶联不仅取决于所涉及通道的生物物理特性,还取决于通道与胞吐装置之间的关系,这在快速和慢速分泌类型之间可能有所不同。钙离子通道在快速释放位点的共定位可能取决于通道与胞吐蛋白之间的生化相互作用。本文的目的是综述关于钙离子通道在胞吐分泌中的结构和功能的最新研究。我们讨论了钙离子通道参与的特定分泌类型,包括中枢神经传递、内分泌和神经内分泌分泌,以及分级电位突触处的传递。几种不同的钙离子通道亚型参与这些分泌类型,它们的功能可能涉及与胞吐装置的多种关系。阐明钙离子通道结构与功能之间的关系是我们理解胞吐分泌基本过程的核心。