Voltage-and frequency-dependent block of diltiazem on the slow inward current and generation of tension in frog ventricular muscle

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Abstract
The effects of a new “Ca2+-antagonist”, diltiazem, were studied in frog ventricular myocardium. The single sucrose gap voltage clamp technique was used to control membrane potential and measure membrane current and tension. Diltiazem had no effect on the resting potential, but reduced the slow inward current (Isi) and increased the net outward current. Membrane conductance measurements suggest that the increase in the total membrane current may be due to the suppression of a maintained inward current. The blocking action of diltiazem is frequencydependent such that at higher frequencies of stimulation, the steady-state amplitude of twitch is reduced. The diltiazem-induced suppression of tension and Isi could be partially reversed by hyperpolarizing the surface membrane for brief intervals. These results suggest that diltiazem blocks Isi in a volgate- and time-dependent manner. These effects of diltiazem on Isi seem to be, in part, responsible for the tension-suppressant effect of the drug.