Ca²⁺ Release Channel of Sarcoplasmic Reticulum: Characterization of the Regulatory Sites

Abstract

This chapter focuses on an unresolved aspect of muscle function, namely, how does sarcoplasmic reticulum (SR) release calcium ions, thereby causing muscle to contract? A schematic drawing of a small segment of a muscle cell is depicted in the upper part of Fig. 1. Two key structures in excitation-contraction coupling—the surface membrane, composed of the sarcolemma and transverse (T-)system, and the SR—are shown. SR is an intracellular membrane system whose main function is to regulate muscle contraction and relaxation by releasing and taking up again the released Ca²⁺. Rapid release from skeletal muscle SR is triggered by a surface membrane potential that is thought to be communicated to SR at specialized areas where the SR comes in close contact with the T-tubule, and protein bridges (“feet”) are present which span the gap between the two membrane systems. However, how calcium ions are released from SR has remained an enigma^(1,2) (also see Chapter 22, this book). One hypothesis is that T-tubule depolarization increases in the junctional gap the concentration of a chemical messenger such as Ca²⁺, which then opens a Ca²⁺ -channel in the SR membrane. Another popular hypothesis suggests that the feet are in direct contact with a voltage-sensing molecule in the T-tubule membrane. During T-tubule depolarization the feet undergo a conformational change which regulates the opening of the SR Ca²⁺-channels.