Analysis of caffeine action in single trabeculae of the frog heart.

Effects of caffeine on contractile tension and on intracellular action and resting potentials were examined in single frog heart trabeculae suspended in a rapid perfusion chamber. Trabeculae from atria responded more readily than those from ventricles and were therefore studied in greater detail. Both the contracture and twitch responses, the one obtained at high (greater than or equal to 10mM), the other at low (less than or equal to 10mM) caffeine concentrations, consisted of a transient tension rise followed by a maintained phase of lower, but still enhanced, tension. The hypothesis was tested that the transient response is due to the release of calcium from the sarcoplasmic reticulum (s.r.) whereas the maintained tension results from enhanced calcium influx through the cell surface. Support for these ideas was obtained by examining the response to step changes of external calcium and caffeine concentrations, applied in various combinations, simultaneously and in sequence. It also emerged tht the effects on twitch tension of calcium derived from (a) s.r. discharge and (b) influx are additive, to a first approximation. A test procedure for monitoring the s.r. store content was evolved to follow the accumulation of s.r. calcium after a preceding depletion. The results obtained, and others, suggest that the s.r. calcium pump can be operative in atrial heart cells and capable, after store depletion, of reabsorbing up to some 40% of calcium activating a twitch, the remainder being, presumably, extruded from the cells.