Wickman K, Clapham D E
Department of Pharmacology, Mayo Foundation, Rochester, Minnesota, USA.
Physiol Rev. 1995 Oct;75(4):865-85. doi: 10.1152/physrev.1995.75.4.865.
Ion channels are poised uniquely to initiate, mediate, or regulate such distinct cellular activities as action potential propagation, secretion, and gene transcription. In retrospect, it is not surprising that studies of ion channels have revealed considerable diversities in their primary structures, regulation, and expression. From a functional standpoint, the various mechanisms coopted by cells to regulate channel activity are particularly fascinating. Extracellular ligands, membrane potential, phosphorylation, ions themselves, and diffusible second messengers are all well-established regulators of ion channel activity. Heterotrimeric GTP-binding proteins (G proteins) mediate many of these types of ion channel regulation by stimulating or inhibiting phosphorylation pathways, initiating intracellular cascades leading to elevation of cytosolic Ca2+ or adenosine 3',5'-cyclic monophosphate levels, or by generating various lipid-derived compounds. In some cases, it seems that activated G protein subunits can interact directly with ion channels to elicit regulation. Although there is currently little direct biochemical evidence to support such a mechanism, it is the working hypothesis for the most-studied G protein-regulated ion channels.
离子通道在启动、介导或调节诸如动作电位传播、分泌和基因转录等不同的细胞活动方面具有独特的作用。回顾过去，离子通道的研究揭示了其一级结构、调节和表达方面存在相当大的多样性，这并不奇怪。从功能的角度来看，细胞用于调节通道活性的各种机制尤其引人入胜。细胞外配体、膜电位、磷酸化、离子本身以及可扩散的第二信使都是已被充分证实的离子通道活性调节剂。异源三聚体GTP结合蛋白（G蛋白）通过刺激或抑制磷酸化途径、启动导致胞质Ca2+或腺苷3',5'-环磷酸水平升高的细胞内级联反应，或通过产生各种脂质衍生化合物，介导许多这类离子通道调节。在某些情况下，似乎活化的G蛋白亚基可以直接与离子通道相互作用以引发调节。尽管目前几乎没有直接的生化证据支持这种机制，但它是大多数研究的G蛋白调节离子通道的工作假设。
