Physiology and Pharmacology of Ryanodine Receptor Calcium Release Channels

Angela F. Dulhunty, Philip G Board, Nicole A Beard, Marco G Casarotto

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Ryanodine receptor (RyR) ion channels are essential for skeletal and cardiac muscle function. Their knockout leads to perinatal death from respiratory and cardiac failure. Acquired changes or mutations in the protein cause debilitating skeletal myopathy and cardiac arrhythmia which can be deadly. Knowledge of the pharmacology of RyR channels is central to developing effective and specific treatments of these myopathies. The ion channel is a >2.2MDa homotetamer with distinct structural and functional characteristics giving rise to a myriad of regulatory sites that are potential therapeutic targets. Australian researchers have been intimately involved in the exploration of the proteins since their identification in the mid-1980s. We discuss major aspects of RyR physiology and pharmacology that have been tackled in Australian laboratories. Specific areas of interest include ultrastructural aspects and mechanisms of RyR activation in excitation-contraction (EC) coupling and related pharmacological developments, regulation of RyRs by divalent cations, by associated proteins including the FK506-binding proteins, by redox factors and phosphorylation. We consider adverse effects of anthracycline chemotherapeutic drugs on cardiac RyRs. Phenotypes associated with RyR mutations are discussed with current and developing therapeutic approaches for treating the underlying RyR dysfunction.

Original languageEnglish
Pages (from-to)287-324
Number of pages38
JournalAdvances in Pharmacology
Volume79
DOIs
Publication statusPublished - 2017

Fingerprint

Ryanodine Receptor Calcium Release Channel
Pharmacology
Muscular Diseases
Ion Channels
Tacrolimus Binding Proteins
Excitation Contraction Coupling
Mutation
Proteins
Anthracyclines
Divalent Cations
Respiratory Insufficiency
Oxidation-Reduction
Cardiac Arrhythmias
Myocardium
Skeletal Muscle
Heart Failure
Phosphorylation
Research Personnel
Phenotype
Therapeutics

Cite this

Dulhunty, Angela F. ; Board, Philip G ; Beard, Nicole A ; Casarotto, Marco G. / Physiology and Pharmacology of Ryanodine Receptor Calcium Release Channels. In: Advances in Pharmacology. 2017 ; Vol. 79. pp. 287-324.
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Physiology and Pharmacology of Ryanodine Receptor Calcium Release Channels. / Dulhunty, Angela F.; Board, Philip G; Beard, Nicole A; Casarotto, Marco G.

In: Advances in Pharmacology, Vol. 79, 2017, p. 287-324.

Research output: Contribution to journalArticle

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