Ryanodine receptor and junctional membrane structure

Abstract

In excitable cell types, activation of cell-surface Ca²⁺ channels triggers Ca²⁺ release from the endplasmic or sarcoplasmic reticulum (ER/SR). This Ca²⁺ signal amplification, termed Ca²⁺-induced or voltage-induced Ca²⁺ release (CICR/VICR), requires the ryanodine receptor as an intracellular Ca²⁺ channel, which is predominantly localized in the junctional membrane complex between the plasma membrane and the ER/SR. Junctophilin is an ER/SR membrane protein that contributes to the formation of the junctional membrane structure. Ryanodine receptor and junctophilin subtypes are derived from distinct genes and show different tissue-specific expression. Recent gene-knockout studies have defined physiological functions of both Ca²⁺ release via ryanodine receptors and junctional membrane structures constituted by junctophilins in excitable cells. Moreover, several human genetic diseases are caused by mutations at the ryanodine receptor and junctophilin subtype genes.