The effects of ryanodine on calcium-overloaded sheep cardiac Purkinje fibers.

Prolonged exposure to high concentrations of strophanthidin produces an initial increase followed by a subsequent decrease of twitch tension. The slow decrease is termed calcium overload. The aim of the present work was to investigate the effects of ryanodine (an inhibitor of calcium release from the sarcoplasmic reticulum) on calcium-overloaded sheep cardiac Purkinje fibers. The fibers were voltage-clamped, and tension was measured while monitoring the intracellular calcium concentration with the photoprotein aequorin. When strophanthidin (10 microM) was applied to produce calcium overload, a depolarizing pulse produced twitch, and tonic components of tension and repolarization produced an aftercontraction. These components of tension were accompanied by corresponding increases of aequorin light. Ryanodine (1 microM) gave a transient increase of twitch tension. The twitch then decreased to very low levels. The aftercontraction and its corresponding aequorin light signal decreased monotonically on application of ryanodine. It has been suggested that the fall of force in calcium overload may be due to random diastolic release of calcium from the sarcoplasmic reticulum interfering with subsequent systolic calcium release. We suggest that the positive inotropic effect of ryanodine can be explained if ryanodine decreases the diastolic release of calcium. The transient positive inotropic effect of ryanodine reported here is therefore consistent with the hypothesis that the fall of force in calcium overload is due to diastolic calcium oscillations.