Effects of catecholamines and cyclic amp on excitation--contraction coupling in isolated skeletal muscle fibres of the frog.

1. In skeletal muscle the presence of a positive inotropic effect induced by adrenaline has been a matter of controversy. If it exists, it could be due to catecholamines acting on the actomyosin system, on the sarcoplasmic reticulum (SR) Ca2+ pump or on the release or influx of Ca2+. We investigated these possibilities by using intact, split and skinned skeletal muscle fibres. We also investigated whether adrenaline acts directly or through cyclic AMP. 2. Catecholamines produced an increase in twitch tension and in maximum rates of tension development and tension decay. The inotropic effect took 3 min to appear and 8 min to reach its maximum level. With tetanic stimulations the extra force appeared only at the beginning of the tetanus while approaching the same maximum level, and tended to disappear faster, the higher the frequency of stimulation. At 4 shocks/sec the peak twitch tension with catecholamines decreased during the first seven to ten twitches and became steady afterwards at a level that was still greater than the control. 3. Resting and action potentials showed no important changes in the presence of adrenaline that could explain the inotropic effect. 4. In split fibres the force produced with the release of Ca2+ from the SR by caffeine was 60-100% larger when cyclic AMP was added to the previous loading solution. In skinned fibres adrenaline given directly to the interior of the cell produced no changes in contraction--relaxation cycles induced by fixed amounts of Ca2+ applied with a pipette. 5. These results strongly suggest that catecholamines through cyclic AMP stimulate the SR Ca2+ pump, increasing thereby the concentration of Ca2+ within the SR. This extra Ca2+ when released during subsequent activation may produce the increase in twitch tension.