Comparative studies on anesthetic properties of primacaine HC1.
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The effects of verapamil and its optical isomers on the electrical and mechanical characteristics of single muscle fibers of Callinectes danae were studied. Verapamil (10-20 microng/ml) blocked the procaine- and TEA-induced spikes; the blockade was preceded by reduction in the rate of rise of the upstroke and increase in the duration of the action potentials. Inhibition of Ba-spikes required higher concentrations of verapamil (greater than 50 microng/ml). These concentrations reduced the amplitude of the normally occurring graded electrogenic membrane responses and reduced the rate of development of the current-induced tensions. With lower concentrations (10-30 microng/ml) verapamil enhanced the negative afterpotentials and the peak amplitude of the local contractions elicited by depolarizing current pulses, while the graded membrane responses were not markedly modified. Verapamil (1-100 microng/ml) did not affect the resting membrane potential but increased the effective membrane resistance. Determination of the cable characteristics by DC pulses indicated that verapamil (1-10 microng/ml) shortens the membrane length constant, increases the specific resistivity of the sarcoplasm and, in most cases, increases the membrane time constant. Verapamil (10 microng/ml) induced tension in these crab fibers. The contractions were potentiated in Na-deficient media, by increase in [Ca]0, and by membrane depolarization; "Ca-free" salines depressed, and procaine abolished these contractions. The results suggest that verapamil affects both Ca and K conductances and interferes with the Ca-sequestering mechanisms of these fibers. The (-)-isomer of verapamil was more effective than the (+)-isomer with respect to tension development, prolongation and subsequent blockade of procaine-spikes and enhancement of current-induced after-potentials and contractions.
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