An inhibitory effect of veratridine during tetanic stimulation of the rat diaphragm.

Abstract

The membrane 'labilizer' veratridine (3.7 x 10(-5) M) which potentiates the contractions at twitch (0.1 Hz) stimulation due to multiple discharges, inhibited the tetanic contractions (50 Hz in 10 s) and the simultaneously recorded electromyogram in a use-dependent way, leading to fading of tetanic tension. The effect was equal during indirect and direct stimulation, and could therefore be localized to the excitable sarcolemma. This was confirmed by intracellular recording of action potentials, showing a marked veratridine-induced fallout of action potentials during continuous 50 Hz stimulation, whereas endplate potentials were unaffected. Accordingly, veratridine probably caused a use-dependent inhibition of the Na+ channels of the excitable sarcolemma. The tetanic fade was unaffected by K+ depolarization, increased by hyperpolarization in K(+)-free solution, and decreased by high Ca2+. All these changes of the ionic concentrations inhibited the twitch potentiating effect of veratridine. Since hyperpolarization and increasing the electric field in the membrane with high Ca2+ had opposite effects on the tetanic fade, the field change was probably not the cause of the antagonism in high Ca2+. Instead, a membrane stabilizing effect of high Ca2+ is suggested, since the neutral local anaesthetic benzocaine (1.5 x 10(-4) M), which is also a membrane stabilizing drug, had the same effects as high Ca2+ on the veratridine-induced tetanic fade. The effect of veratrine during tetanic stimulation was partly reversible upon washing. The reversibility was enhanced by high Ca2+ or benzocaine.