{'fraction_non_alphanumeric': 0.029686641011544807, 'fraction_numerical': 0.009895547003848268, 'mean_word_length': 4.9868421052631575, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Sarcolemmal Site of Caffeine+‐s Inotropic Action on Ventricular Muscle of the Frog

We used a procedure to alter rapidly the composition of extracellular fluid, in frog ventricle strips, while recording force development and transmembrane potential. At a driven rate of 3 beats/min, the calcium concentration in the Ringer+-s solution was reduced from the control value of 0.7 mM to 0.025 mM, and force developed by the immediately succeeding beat was reduced to less than 6% of the control value. We found that addition of caffeine (20 mM) to the calcium-poor Ringer+-s solution immediately following this beat caused a restoration of 42% of control force development by the next beat. Contractile force was abolished, in the continued presence of caffeine, on the beat following the further addition of 10 mM manganous chloride to the Ringer+-s solution. Further- more, application of caffeine to the muscle during the course of prolonged contraction (18-second voltage clamp pulse) caused an abrupt increase in force to a new steady state value during the same contraction. From experiments with calcium-buffered Ringer+-s solution (Tris-EGTA), the inotropic action of caffeine was found to be entirely dependent on the extracellular calcium concentration and was lost at or below a value of 10{i M. Prior exposure of the muscle to calcium-rich or calcium-poor media had, in contrast, no effect on the inotropic effect of caffeine. These findings suggest a primarily sarcolemmal site for the inotropic action of caffeine in this tissue. An alternative interpretation, that these results are due to profound alterations in the influx of "trigger" calcium, is not supported by the finding that contractile force can be rapidly graded, during a single depolarization, by grading the extracellular calcium concentration.