Coronado R, Morrissette J, Sukhareva M, Vaughan D M
Department of Physiology, University of Wisconsin School of Medicine, Madison 53706.
Am J Physiol. 1994 Jun;266(6 Pt 1):C1485-504. doi: 10.1152/ajpcell.1994.266.6.C1485.
Membrane depolarization, neurotransmitters, and hormones evoke a release of Ca2+ from intracellular Ca(2+)-storing organelles like the endoplasmic reticulum and, in muscle, the sarcoplasmic reticulum (SR). In turn, the released Ca2+ serves to trigger a variety of cellular responses. The presence of Ca2+ pumps to replenish intracellular stores was described more than 20 years ago. The presence of Ca2+ channels, like the ryanodine receptor, which suddenly release the organelle-stored Ca2+, is a more recent finding. This review describes the progress made in the last five years on the structure, function, and regulation of the ryanodine receptor. Numerous reports have described the response of ryanodine receptors to cellular ions and metabolites, kinases and other proteins, and pharmacological agents. In many cases, comparative measurements have been made using Ca2+ fluxes in SR vesicles, single-channel recordings in planar bilayers, and radioligand binding assays using [3H]ryanodine. These techniques have helped to relate the activity of single ryanodine receptors to global changes in the SR Ca2+ permeability. Molecular information on functional domains within the primary structure of the ryanodine receptor is also available. There are at least three ryanodine receptor isoforms in various tissues. Some cells, such as amphibian muscle cells, express more than a single isoform. The diversity of ligands known to modulate gating and the diversity of tissues known to express the protein suggest that the ryanodine receptor has the potential to participate in many types of cell stimulus-Ca(2+)-release coupling mechanisms.
膜去极化、神经递质和激素可促使细胞内钙储存细胞器（如内质网，在肌肉中为肌浆网，即SR）释放Ca2+。反过来，释放出的Ca2+可触发多种细胞反应。20多年前就已描述了存在Ca2+泵来补充细胞内储存。像雷诺丁受体这种能突然释放细胞器储存Ca2+的Ca2+通道的存在则是更近的发现。本综述描述了过去五年在雷诺丁受体的结构、功能及调节方面取得的进展。众多报告描述了雷诺丁受体对细胞离子和代谢物、激酶及其他蛋白质以及药理剂的反应。在许多情况下，已利用SR囊泡中的Ca2+通量、平面双层中的单通道记录以及使用[3H]雷诺丁的放射性配体结合测定进行了比较测量。这些技术有助于将单个雷诺丁受体的活性与SR Ca2+通透性的整体变化联系起来。关于雷诺丁受体一级结构内功能域的分子信息也已可得。在各种组织中至少存在三种雷诺丁受体亚型。一些细胞，如两栖动物肌肉细胞，表达不止一种亚型。已知可调节门控的配体的多样性以及已知表达该蛋白的组织的多样性表明，雷诺丁受体有可能参与多种类型的细胞刺激 - Ca(2+) - 释放偶联机制。
