Evidence for an Intracellular Ryanodine- and Caffeine-Sensitive Calcium Ion-Conducting Channel in Excitable Tissues

Abstract

In skeletal and cardiac muscle, an action potential triggers the release of calcium ions from the intracellular membrane compartment, sarcoplasmic reticulum (SR), via a ligand-gated, high-conductance “Ca²⁺ release” channel. This channel has been identified as the receptor for the plant alkaloid ryanodine and also shown to be morphologically identical with the large protein structures (“feet”) that span the gap between junctional SR and the muscle surface membrane and T-tubule. The detergent-solubilized Ca²⁺ release channel has been purified from skeletal and cardiac muscle as a tetrameric 30 S protein complex and reconstituted into planar lipid bilayers. The skeletal and cardiac channels conduct monovalent cations in addition to Ca²⁺, are activated by Ca²⁺, and modulated by ATP, Mg²⁺, calmodulin, and the two Ca²⁺ releasing drugs caffeine and ryanodine. Ruthenium red, a polyvalent cation, inhibits the channels at micromolar concentrations. Recently, our laboratory has also obtained evidence for the presence of a 30 S mono- and divalent cation-conducting channel complex in canine and porcine aorta and rat and bovine brain. A similar high molecular weight Ca²⁺ release channel complex may be present therefore, in most, if not all, mammalian excitable tissues.