INTRACELLULAR CALCIUM SIGNALING IN STRIATED-MUSCLE CELLS

Calcium signalling in cells is dependent on a communication between ch annels/ transporters in two membrane structures: the cell membrane and the membranes of endo-and sarcoplasmic reticula (ER/SR). In general, cytosolic Ca2+ can be raised by influx of calcium over the cell membra ne through three types of channels: voltage-, receptor-, and store-ope rated channels (VOCs, ROCs and SOCs). This small Ca2+ influx is most o ften amplified by a Ca2+ release from the ER/SR through two types of c hannels: the IP3-receptor and the ryanodine receptor (RyR), which are huge proteins identified and cloned in recent years. We focus on the ' synaptic' connection between VOCs (L-type calcium channels) and RyRs o f the SR in heart and skeletal muscle. Depolarization of the cell memb rane (an action potential) opens the VOC and moves it in the membrane. One VOC triggers opening of a certain number of underlying RyRs that together release a quantum of calcium from the SR, a calcium spark. Th e communication between the VOC and RyRs is probably achieved primaril y by a mechanical link in skeletal muscle (voltage-controlled calcium release), and by the small inward calcium flux through the VOC in the heart (calcium-induced calcium release, CICR). Conditions as different as heart failure, myasthenia gravis, malignant hyperthermia, and skel etal muscle fatigue, may be examples of deteriorated control or functi on of the RyR.