Analysis of caffeine action in single trabeculae of the frog heart

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Abstract
Effect 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 studied in greater detail. Both the contracture and twitch responses, the one obtained at high (.gtoreq. 10 mM), the other at low (.ltoreq. 10 mM) 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 Ca from the sarcoplasmic reticulum while the maintained tension results from enhanced Ca influx through the cell surface. Support for these ideas was obtained by examining the response to step changes of external Ca and caffeine concentrations, applied in various combinations, simultaneously and in sequence. The effects on twitch tension of Ca derived from SR discharge and influx are additive, to a 1st approximation. A test procedure for monitoring the SR store content was evolved to follow the accumulation of SR Ca after a preceding depletion. Apparently the SR Ca pump can be operative in atrial heart cells and capable, after store depletion, of reabsorbing up to some 40% of Ca activating a twitch, the remainder being, presumably, extruded from the cells.