Ryanodine receptor structure and function in health and disease

Gaetano Santulli, Daniel Lewis, Amedee des Georges, Andrew R. Marks, Joachim Frank

Research output: Chapter in Book/Report/Conference proceedingChapter


Ryanodine receptors (RyRs) are ubiquitous intracellular calcium (Ca2+) release channels required for the function of many organs including heart and skeletal muscle, synaptic transmission in the brain, pancreatic beta cell function, and vascular tone. In disease, defective function of RyRs due either to stress (hyperadrenergic and/or oxidative overload) or genetic mutations can render the channels leaky to Ca2+ and promote defective disease-causing signals as observed in heat failure, muscular dystrophy, diabetes mellitus, and neurodegerative disease. RyRs are massive structures comprising the largest known ion channel-bearing macromolecular complex and exceeding 3 million Daltons in molecular weight. RyRs mediate the rapid release of Ca2+ from the endoplasmic/sarcoplasmic reticulum (ER/SR) to stimulate cellular functions through Ca2+-dependent processes. Recent advances in single-particle cryogenic electron microscopy (cryo-EM) have enabled the determination of atomic-level structures for RyR for the first time. These structures have illuminated the mechanisms by which these critical ion channels function and interact with regulatory ligands. In the present chapter we discuss the structure, functional elements, gating and activation mechanisms of RyRs in normal and disease states.

Original languageEnglish (US)
Title of host publicationSubcellular Biochemistry
PublisherSpringer New York
Number of pages24
StatePublished - 2018

Publication series

NameSubcellular Biochemistry
ISSN (Print)0306-0225


  • Calcium release channel
  • Cryo-EM
  • Endoplasmic reticulum
  • Ryanodine receptor (RyR)
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology
  • Cancer Research


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