Ryanodine receptor

[1] There are three major isoforms of the ryanodine receptor, which are found in different tissues and participate in different signaling pathways involving calcium release from intracellular organelles.

The RYR2 ryanodine receptor isoform is the major cellular mediator of calcium-induced calcium release (CICR) in animal cells.

[4] Ryanodine receptors are very close to mitochondria and calcium release from RyR has been shown to regulate ATP production in heart and pancreas cells.

[18] The breakdown of this feedback mechanism causes uncontrolled release of Ca2+ into the cytoplasm, and increased ATP hydrolysis resulting from ATPase enzymes shuttling Ca2+ back into the sarcoplasmic reticulum leads to excessive heat generation.

[22] Sudden cardiac death in several young individuals in the Amish community (four of which were from the same family) was traced to homozygous duplication of a mutant RyR2 (Ryanodine Receptor) gene.

Ryanodine receptors are multidomain homotetramers which regulate intracellular calcium ion release from the sarcoplasmic and endoplasmic reticula.

[24] They are the largest known ion channels, with weights exceeding 2 megadaltons, and their structural complexity enables a wide variety of allosteric regulation mechanisms.

[25][26] RyR1 cryo-EM structure revealed a large cytosolic assembly built on an extended α-solenoid scaffold connecting key regulatory domains to the pore.

A unique domain inserted between the second and third transmembrane helices interacts intimately with paired EF-hands originating from the α-solenoid scaffold, suggesting a mechanism for channel gating by Ca2+.