The structure, function, and cellular regulation of ryanodine-sensitive Ca2+ release channels

Varda Shoshan-Barmatz, Richard H. Ashley

Research output: Contribution to journalArticlepeer-review

81 Scopus citations


The fundamental biological process of Ca2+ signaling is known to be important in most eukaryotic cells, and inositol 1,2,5-trisphosphate and ryanodine receptors, intracellular Ca2+ release channels encoded by two distantly related gene families, are central to this phenomenon. Ryanodine receptors in the sarcoplasmic reticulum of skeletal and cardiac muscle have a predominant role in excitation-contraction coupling, but the channels are also present in the endoplasmic reticulum of noncontractile tissues including the central nervous system and the immune system. In all, three highly homologous ryanodine receptor isoforms have been identified, all very large proteins which assemble as (homo)tetramers of ∼2 MDa. They contain large cytoplasmically disposed regulatory domains and are always associated with other structural or regulatory proteins, including calmodulin and immunophilins, which can have marked effects on channel function. The type 1 isoform in skeletal muscle is electromechanically coupled to surface membrane voltage sensors, whereas the remaining isoforms appear to be activated solely by endogenous cytoplasmic second messengers or other ligands, including Ca2+ itself ("Ca2+-induced Ca2+ release"). This review concentrates on ryanodine receptor structure-function relationships as probed by a variety of methods and on the molecular mechanisms of channel modulation at the cellular level (including evidence for the regulation of gene expression and transcription). It also touches on the relevance of ryanodine receptors to complex cellular functions and disease.

Original languageEnglish
Pages (from-to)185-270
Number of pages86
JournalInternational Review of Cytology
StatePublished - 1 Jan 1998


  • Calcium release
  • Ion channels
  • Ryanodine receptor
  • Sarcoplasmic reticulum
  • Striated muscle

ASJC Scopus subject areas

  • Histology
  • Cell Biology


Dive into the research topics of 'The structure, function, and cellular regulation of ryanodine-sensitive Ca2+ release channels'. Together they form a unique fingerprint.

Cite this