EFFECTS OF RYANODINE AND CYCLOPIAZONIC ACID ON SKINNED FIBERS OF VENTRICULAR MYOCARDIUM FROM NEONATAL AND ADULT RATS

1. We examined the effects of ryanodine and cyclopiazonic acid (CPA) o n Ca2+ release from myocardial sarcoplasmic reticulum (SR) with skinne d fibers of neonatal rat ventricular myocardium. 2. Both ryanodine and CPA concentration dependently reduced the caffeine-induced tension in skinned fibers with functional SR preserved; 1 mu M ryanodine and 20 mu M CPA reduced the caffeine-induced tension to less than 20% of cont rol values. 3. Both agents had no effect on the Ca2+-tension relation of skinned fibers without functional SR. 4. These results suggest that ryanodine and CPA inhibit Ca2+ release from the SR and Ca2+ uptake in to it in neonatal myocardia. 5. Thus, less-negative inotropic effects of ryanodine and CPA on neonatal myocardia compared with those on adul t myocardia (Agata et al., 1993; Tanaka and Shigenobu, 1989) could not be ascribed to lack of drug effects on the SR per se. (C) 1998 Elsevi er Science Inc.