RAT ATRIAL MUSCLE RESPONSES WITH CAFFEINE - DOSE-RESPONSE, FORCE FREQUENCY, AND POSTREST CONTRACTIONS

Caffeine has been reported to have a positive and (or) a negative inot ropic effect on cardiac muscle. In this study, the force-frequency and postrest characteristics of rat atrium were studied in the presence o f caffeine (1.0 - 10 mM) to see if the interval between beats affected the response of cardiac muscle to caffeine. When stimulation frequenc y was 0.5 or 2.0 Hz, there was a positive followed by a negative inotr opic response with 1, 5, or 10 mM caffeine. Incomplete relaxation occu rred under these circumstances, giving rise to contracture. At low fre quency of stimulation (0.1 Hz) caffeine had only a negative inotropic effect, and this effect was greater with 1 mM caffeine than with 5 mM caffeine. In the absence of caffeine, when stimulation at 0.5 or 3 Hz was interrupted, a pause of 2 - 20 s resulted in potentiation. When ca ffeine was present (2.0 mM), postrest potentiation was severely attenu ated, but the steady-state contraction amplitude within the range 0.5 - 3.0 Hz was not different. These results are consistent with the hypo thesis that caffeine induces a leak of Ca2+ from the sarcoplasmic reti culum, and this Ca2+ is extruded from the cell, possibly by Na+/Ca2+ e xchange. Sarcoplasmic reticular uptake of Ca2+ and the translocation t o release sites appear not to be affected by caffeine within 1 - 5 mM concentrations.