Ryanodine receptor

Ryanodine receptors (RyRs) form a class of intracellular calcium channels in various forms of excitable animal tissue like muscles and neurons.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. Ryanodine receptors (RyRs) form a class of intracellular calcium channels in various forms of excitable animal tissue like muscles and neurons.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. The ryanodine receptors are named after the plant alkaloid ryanodine, to which they show a high affinity. There are multiple isoforms of ryanodine receptors: Ryanodine receptors mediate the release of calcium ions from the sarcoplasmic reticulum and endoplasmic reticulum, an essential step in muscle contraction. In skeletal muscle, activation of ryanodine receptors occurs via a physical coupling to the dihydropyridine receptor (a voltage-dependent, L-type calcium channel), whereas, in cardiac muscle, the primary mechanism of activation is calcium-induced calcium release, which causes calcium outflow from the sarcoplasmic reticulum. It has been shown that calcium release from a number of ryanodine receptors in a ryanodine receptor cluster results in a spatiotemporally restricted rise in cytosolic calcium that can be visualised as a calcium spark. Ryanodine receptors are very close to mitochondria and calcium release from RyR has been shown to regulate ATP production in heart and pancreas cells. Ryanodine receptors are similar to the inositol trisphosphate (IP3) receptor, and stimulated to transport Ca2+ into the cytosol by recognizing Ca2+ on its cytosolic side, thus establishing a positive feedback mechanism; a small amount of Ca2+ in the cytosol near the receptor will cause it to release even more Ca2+ (calcium-induced calcium release/CICR). However, as the concentration of intracellular Ca2+ rises, this can trigger closing of RyR, preventing the total depletion of SR. This finding therefore indicates that a plot of opening probability for RyR as a function of Ca2+ concentration is a bell-curve. Furthermore, RyR can sense the Ca2+ concentration inside the ER/SR and spontaneously open in a process known as store overload-induced calcium release (SOICR). RyRs are especially important in neurons and muscle cells. In heart and pancreas cells, another second messenger (cyclic ADP-ribose) takes part in the receptor activation. The localized and time-limited activity of Ca2+ in the cytosol is also called a Ca2+ wave. The building of the wave is done by RyRs form docking platforms for a multitude of proteins and small molecule ligands.The cardiac-specific isoform of the receptor (RyR2) is known to form a quaternary complex with luminal calsequestrin, junctin, and triadin. Calsequestrin has multiple Ca2+ binding sites and binds Ca2+ ions with very low affinity so they can be easily released.