Ryanodine Receptor Structure and Function in Health and Disease.

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