Stabilizing-labilizing effects of reserpine, chlorpromazine, tetracaine, and quinidine on frog skeletal muscle fibers

Summary

In order to characterize the interaction of reserpine, chlorpromazine, tetracaine, and quinidine with membrane phenomena, electrophysiological studies were performed on frog skeletal muscle fibers under various ionic environments. In addition the influence of these drugs on the contractility of the frog skeletal muscle was investigated.

• 1. Measurements of intracellular membrane potentials of the sartorius muscle fibers revealed that tetracaine, quinidine, chlorpromazine, and reserpine diminished the depolarizing action of high [K⁺]₀: while the resting potential in normal Ringer's solution fell from −90 mV to −9.3 mV when 100 mM NaCl was replaced by the same amount of KCl, a time and dose-dependent increase of the membrane potential depolarized by potassium was observed after addition of these drugs. The order of the polarizing potency was reserpine > chlorpromazine > tetracaine > quinidine.

• 2. Maximal stabilizing effects (i. e. increase of the membrane potential in 100 mM KCl Ringer's solution to more negative values) were observed with the following drug concentrations (20 min incubation time): reserpine 10⁻⁴ M (13 mV increase); chlorpromazine 3 X10⁴ M (21 mV increase); quinidine 3 × 10⁻³ M (15 mV increase); tetracaine 10⁻²M (28 mV increase). At higher concentrations, reversion of the polarizing effects occurred as a consequence of labilization of the muscle membrane.

• 3. Evidence for such a biphasic effect, i.e. stabilizing-labilizing effect of the drugs came also from measurements of the relative membrane resistanceR _r. In 100 mM KCl Ringer's solution tetracaine in concentrations up to 10⁻³ M caused an absolute increase. Higher concentrations produced again a subsequent fall ofR _r. Quinidine, chlorpromazine and reserpine inhibited only the time-dependent decrease ofR _r normally found in control preparations.

• 4. In chloride-deficient 112 mM KCH₃S0₄ Ringer's solution, tetracaine produced a several fold higher increase ofR _r. Under these experimental conditions also quinidine and chlorpromazine caused an absolute enhancement ofR _r, but not reserpine. These findings indicate that chiefly the potassium conductanceg _K of the muscle fiber membrane was affected by tetracaine, chlorpromazine, and quinidine.

• 5. Tetracaine, quinidine, chlorpromazine, and reserpine inhibited the KCl-induced contractions of the sartorius muscle as well as the acetylcholine-induced mechanical activity of the frog rectus abdominis muscle.

• 6. From the results it is concluded that the different drugs used in this investigation may exert their effects by a rather common mechanism, i.e. via membrane stabilization; this is indicated by the observed impairment of the membrane permeability for cations.