ryanodine and pyrithione

To explore whether the differential effects of Zn2+ on ryanodine binding to the sarcoplasmic reticulum (SR) of skeletal and cardiac muscles resulted from different permeability of the SR to Zn2+.. [3H]ryanodine binding assays were performed to examine the effect of Zn2+ on ryanodine binding to the SR in the presence of pyrithione sodium (PyNa), a specific Zn2+ ionophore.. As a control, PyNa up to 50 micromol/L did not induce any effect on ryanodine binding to the SR of cardiac muscle. But PyNa 1-100 micromol/L increased ryanodine binding in skeletal muscle with maximum binding (222.2+/-20.9 % of the control) and inhibited ryanodine binding to 50 % of the control at about 500 micromol/L. In the presence of PyNa 10 and 50 micromol/L the dose-dependence of the effect of Zn2+ in cardiac muscle was still monophasic and not changed by PyNa, while the biphasic effect of Zn2+ in skeletal muscle became monophasic.. Different permeability of the SR to Zn2+ may account for the differential effects of Zn2+ on ryanodine binding in skeletal and cardiac muscles. PyNa is not a strictly specific Zn2+ ionophore.

Topics: Animals; Dose-Response Relationship, Drug; Ionophores; Myocardium; Organ Specificity; Pyridines; Rabbits; Ryanodine; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum; Thiones; Zinc