Effects of ryanodine on a myocardial membrane vesicular fraction

The effects of ryanodine on calcium transport were examined on a microsomal fraction isolated from guinea pig atrial muscle by sucrose density ultracentrifugation. The Ca+2 binding capacity of the fraction was sufficient to account for relaxation and was unaltered by the addition of 5x10(-5)M ryanodine. Exposure of the sarcoplasmic reticulum (SR) to concentrations of ryanodine which produce negative inotropy significantly reduced ATP-dependent calcium transport which was associated with a significant increase in the Ca+2 activated ATPase activity. The effect of ryanodine was to reduce the Ca/P ratio by 50%. These results suggest that the negative inotropic effect of ryanodine in guinea pig atrium is associated with the uncoupling of Ca+2 transport from ATP hydrolysis.