The effects of verapamil on tetanic contractions of frog's ckeletal muscle

The effects of the organic calcium channel antagonist, verapamil, were tested on twitches and tetanic contractions (100 Hz, 2 sec) in frog toe muscles. At low concentrations (3 × 10^-6 M), verapamil had no effect on the maximum amplitudes of twitches, but significantly reduced the size of the tetanic responses. This depression was observed as an inability to maintain the maximum tetanic tension for more than 0.5 sec. With increasing concentrations up to 10^-4 M of verapamil, its depressant effect on tetanic responses gradually increased, and at very high concentrations (10^-4 M) of verapamil, twitches were also blocked. Intracellular microelectrode recordings showed that there was no block of the action potentials during the stimulus train at the concentration of 3 × 10^-6 M of verapamil. These results support the concept that during tetanic responses, the voltage sensitive Ca²⁺ channels in the t-tubules open and the Ca²⁺ ions entering via these channels are required to maintain the full strength of the contraction. At higher concentrations, verapamil blocked Na⁺ action potentials during the stimulus trains in a concentration and use-dependent manner.