Abstract
The ryanodine receptor (RyR) releases Ca ions from the SR lumen to the cytoplasm as an Excitation-Contraction coupling mechanism of the cardiac myocytes. The RyR channel activities are physiologically or pathophysiologically regulated by various cytosolic biochemical molecules. Here we review the molecular mechanisms on the intracellular regulation we found thus far. (1) Spermine of a polyamine is present in cardiac myocyte. Cytoplasmic spermine formed a nonlinear current-voltage relation in the RyR channel in which the outward Ca current from the cytoplasm to the SR lumen was blocked. This inwardly-rectification could suppress a counterflow of cytoplasmic Ca ion to the SR lumen during the muscle contraction. (2) Phosphorylation of the cardiac RyR by cAMP-dependent protein kinase A (PKA) increased the channel activity. This increase in the RyR channel activities by the phosphorylation was due to the loss of sensitivity to the cytoplasmic Mg ion of the phosphorylated RyR molecule, which could contribute to the positive inotropic effect in the heart via the sympathetic nerve stimulation. (3) Sphingosylphosphatidylcholine (SPC) is metabolized from sphingomyelin of a minor sarcolemmal phospholipid during the apoptosis and the hyperlipidemia. The RyR channels were blocked by the cytoplasmic SPC. (4) Lysophosphatidylcholine (LPC) is metabolized from phosphatidylcholine of a major sarcolemmal phospholipid during the cardiac ischemia. The RyR channels were activated by LPC. [Jpn J Physiol 55 Suppl:S127 (2005)]
