Enhancement of Ca²⁺ release channel activity by phosphorylation of the skeletal muscle ryanodine receptor

Abstract

The Ca" release channel of rabbit skeletal muscle sarcoplasmic reticulum (SR) can be phosphorylated by membrane associated protein kinase(s) utilizing endogenously synthesized or exogenously added ATP. The channel protein has been enriched in non-phosphorylated and phosphorylated form from heavy SR following solubilization with CHAPS (3-[(3cholamidopropyI)dimethylammonio-l-propane-sulfonate) and ultracentrifugation on a linear sucrose/CHAPS gradient. Reconstitution of the isolated channels into planar bilayers shows that phosphorylation enhances the open probability by increasing the sensitivity towards micromolar Ca" and ATP. The phosphorylation induced enhancement of the channel activity can be reversed by purified protein phosphatase 2A.

Ryanodine receptors are involved in muscarinic antinociception in mice

“…The prevention of physostigmine and oxotremorine antinociception produced by ryanodine was dosedependently reversed by co-administration of chloro-mcresol (4-Cmc), an agonist of RyR [17], further suggesting the involvement of RyRs in muscarinic antinociception. It should also be taken into account that compounds able to activate RyR, such as caffeine, are endowed with central antinociceptive properties [10,26,29].…”

Involvement of JAK2 and Src kinase tyrosine phosphorylation in human growth hormone-stimulated increases in cytosolic free Ca2+ and insulin secretion

“…CICR via RyRs is regulated by phosphorylation of the intracellular Ca 2ϩ release channels, leading to increased channel opening (19,24,33). We showed previously that hGH stimulation of ␤-cell proliferation is associated with an increase of the cytoplasmic Ca 2ϩ concentration ([Ca 2ϩ ] i ) (43) and that the hGH-induced elevation of [Ca 2ϩ ] i involves tyrosine phosphorylation of RyRs in BRIN-BD11 ␤-cells (60).…”

Removal of Mg2+ inhibition of cardiac ryanodine receptor by palmitoyl coenzyme A

“…For example, the cytosolic free Mg2' in the vicinity of the cardiac ryanodine receptor may be lowered below the cellular average by active Mg2+ removal [14]. Furthermore, a phosphorylation event [15], an associated protein [ 161, or a cytosolic component may increase the Ca2' sensitivity of the channel in the presence of Mg2+. In the present report, we explored the latter hypothesis and showed that palmitoyl CoA is a potent activator of the cardiac ryanodine receptor that may directly bind to a site in the channel controlling Ca" dependent gating.…”