Abstract
In this study the calcium antagonist drug diltiazem was found to produce twitch potentiation, lower the mechanical threshold potential and block inward calcium currents in bullfrog skeletal muscle fibers. Under tonic conditions (stimulation either every 1 or 2 min) high concentrations of diltiazem were required to enhance twitch tension (ED50 = 249 microM) and block calcium currents (IC50 = 190 microM). In addition, 100 microM diltiazem lowered the mechanical threshold rheobase potential from -49.3 to -57.0 mV. At higher rates of stimulation, concentrations of diltiazem as low as 1 and 10 microM, which had no tonic action, were found to produce twitch potentiation and calcium channel block, respectively. Onset and washout of tonic and frequency-dependent actions of diltiazem on twitch and current amplitude occurred over a similar time course. It is proposed that the mechanical potentiation, as well as the calcium channel block produced by diltiazem, result from the interaction of diltiazem with the same or similar receptor site(s).
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Action of diltiazem on excitation-contraction coupling in bullfrog skeletal muscle fibers.
