Effects of the calcium channel agonist, Bay K 8644, on the mechanical output of skeletal muscle fibers

Abstract

1. 1. The effects of the calcium agonist, Bay K 8644, on the mechanical output of skeletal muscle were studied in frog semitendinosus fiber bundles and in whole sartorius muscles. 2. 2. Low concentrations of Bay K 8644 (≤ 1 μM) had no significant influence on isometric twitches. Concentrations between 5-20 μM increased peak tension by 28.6 ± 2.9% while higher concentrations (≥ 50 μM) initially increased then depressed twitches by 70 ± 3.5%. 3. 3. 10 μM Bay K 8644 also increased peak tension developed during low frequency stimulation (i.e. ≤40 Hz), slightly depressed high frequency contractions (i.e. ≥ 80 Hz) but did not reduce maximal tetanic tension which occurred at about 60 Hz. 4. 4. Potentiation of twitches and low frequency tetani and depression of high frequency tetani by Bay K 8644 were partially antagonized by nifedipine (10 μM), low extracellular calcium and D-600 (5 μM). These conditions did not, however, block the depressant actions of ≥ 50 μM Bay K 8644. 5. 5. In skinned fibers, 10 μM Bay K 8644 had no effect on resting or maximal Ca 2+ activated tension. Also, 10 μM Bay K 8644 had no effect on caffeine contractures when added to the previous Ca 2+ loading solution. 6. 6. These results suggest that Bay K 8644 has both positive and negative inotropic actions on isolated skeletal muscle, which are dependent on drug concentration and muscle activation pattern.