The SR is the Ca2+-storage compartment of muscle. It forms a network in the sarcoplasm so that each fiber is surrounded by the reticulum and thereby has easy access to Ca2+. The SR widens at its two ends forming terminal sacs, called cisternae. A functional unit is a triad, consisting of two cisternae belonging to two adjacent SR and of one transverse (T) tubule in between (Fig. SR1). The distance between the terminal cisternae and the T-tubule is 10-15 nm. This gap is spanned by "foot structures". In frog muscle the transverse tubules are located at the level of the Z line, and in mammalian muscles they are located at the junction of A and I bands.
Fig. SR1. Electron micrograph of T-tubule and SR junction. (From Chu et al., 1987; with permission from Arch. Biochem. Biophys. 258, 13-23, 1987, by Academic Press). The transverse tubule (TT) is flanked by two terminal cisternae of SR. The arrows point to the foot structures. LT, longitudinal tubule of SR.
Fig. SR2 is a scheme of the SR and T-tubule junction. The T-tubule is shown invaginating from the sarcolemma. The foot structure spans the gap between the terminal cisternae and T-tubule. Within the SR, Ca2+ is bound to calsequestrin, a protein that is anchored to the inner membrane of the terminal cisternae. Upon muscle stimulation, Ca2+ leaves the terminal cisternae and binds to troponin-C in the sarcoplasm to initiate the contraction process (see also Fig, EC2). Until the muscle is stimulated, Ca2+ is continuously released from the terminal cisternae. However, a part of the Ca2+ in the sarcoplasm is recaptured by the longitudinal part of the SR; the Ca2+ pump is responsible for the Ca2+ uptake and ATP supplies the energy. Once Ca2+ is inside the longitudinal tubules, it diffuses back to the terminal cisternae, where it is bound to calsequestrin, at the storage site. A 30-kDa calsequestrin-binding protein (Yamaguchi and Kasai, 1998) regulates the binding of Ca2+ to calsequestrin.
Fig. SR2. Scheme of T-tubule and SR junction (From Paul and Heiny, Copyright 1993, reproduced with permission of Lippincott, Williams & Wilkins).
.The terminal cisternae contain the Ca2+ release channels of the SR. That channel is a very large protein (MW about 2 million) that spans the entire SR membrane thickness and protrudes up to the T-tubule. The protruding hydrophilic domain of the channel was first visualized in electron micrographs as foot structures (Franzini-Armstrong and Nunzi, 1983). The Ca2+ release channel, also called as the junctional foot protein, was identified as a ryanodine receptor. It contains a central axial channel and four radial conduits. Ca2+ from SR enters the sarcoplasm at the junction via the four conduits. As the Ca2+ channel opens, Ca2+ leaves the SR, calsequestrin releases Ca2+, and more Ca2+ moves out into the sarcoplasm.
The crystal structure of the Ca2+ - ATPase of skeletal muscle SR has been solved (Toyoshima et al., 2000) with two Ca2+ bound in the transmembrane domain which comprises 10 a-helices. The two Ca2+ are located side by side and are surrounded by four transmembrane helices. The crystallographic and biochemical data suggest that large domain movements take place during Ca2+ transport by the Ca2+ -pump ATPase.
Signal transduction between T-tubule and SR-junction: The dihydropyridine (DHP) receptors of the T-tubule and the Ca2+-release channels of the SR terminal cisternae are participating in signal transduction. The DHP receptors act as voltage sensors: as an action potential propagates over the T-tubules (see Fig. EC2) charged regions of the receptor molecule rapidly move and cause a conformational change in the receptor. The DHP receptors and the Ca2+-release channels are in direct apposition at the junction. The conformational change in the DHP receptors may lead to the opening of the Ca2+-release channels. Several hypotheses have been proposed to connect the measured charge movements in the DHP receptors to Ca2+-release from SR.
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