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1. The relationship between active force and stimulation frequency (0-25-5/sec) was studied at 36-37 degrees C in isolated papillary muscles of the rabbit. 2. The muscle's force producing capability at a given frequency was determined as the isometric twitch response to a test stimulus that was applied at various times after a priming period. The optimum contractile response was obtained at an interval of 0-8 sec between the test pulse and the last stimulus of the priming period. 3. The optimum contractile response exceeded the steady-state twitch amplitude at all stimulation frequencies higher than 1/sec. While the steady-state twitch resonse declined at frequencies higher than 4/sec, the optimum contractile response was steadily increased as the stimulation frequency was raised. 4. The optimum contractile response was also determined after priming the muscle with a sinusoidal a.c. pulse (field strength, 10 V (r.m.s.)/cm; frequency, 20 c/s; duration, 2-5 sec). The optimum contractile response obtained after a.c. stimulation was 2-2 times greater than the maximal steady-state response. Its absolute value was 67-3+/-6-1 mN/mm2 (mean +/-S.E. of mean, n = 6). 5. The twitch potentiation produced by priming the muscle at a given frequency decayed exponentially in two phases after optimum contractile response had been attained. The time constants of the two phases, determined after a.c. stimulation, were 2-6+/-0-8 (n = 4) and 92-0+/-13-3 sec (n = 7), respectively. 6. The optimum contractile response determined at various stimulation frequencies was linearly related to the fraction of time during which the cell membrane was depolarized (beyond -40 mV) by the action potentials. 7. The results are interpreted in terms of a two-component model of the metabolism of activator calcium in the excitation-contraction coupling.
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