Sarcolemmal sodium permeability and contractile force of guinea pig papillary muscle: effects of germitrine.

The action potential of guinea pig papillary muscle exposed to the ceveratrum alkaloid germitrine (2 mugM) is followed by a long-lasting after-depolarization (maximal amplitude, 8 mV; half-time of decay, 32 seconds; total duration, approximately 75 seconds). This after-depolarization interrupts the terminal phase of repolarization. During repetitive stimulation (0.1-1.0 Hz; 80 nM germitrine) the after-depolarizations that follow consecutive action potentials are summed, causing persistent depolarization of up to 10 mV. The after-depolarization is reversibly abolished by tetrodotoxin (TTX). Test contractions evoked at various times during or after the germitrine-induced after-depolarization reveal a phase during which the ability of the muscle to develop force is transiently increased. This positive inotropic influence reaches its maximum 1 minute after the conditioning stimulus and thereafter decays with a half-time 4.8 times longer than the half-time of decay of the after depolarization. It is reversibly abolished by TTX and augmented by dihydro-ouabain (DHO). We conclude: Germitrine induces an after-depolarization by prolonging dramatically the Na permeability component which is mediated by the fast Na channels and normally restricted to the first few milliseconds of the action potential. The germitrine-induced selective and persistent increase of sarcolemmal sodium permeability (PNA) causes a positive inotropic effect, probably because intracellularly accumulating Na ions exchange for extracellular Ca ions.

The effects of protoveratrine and germines on the release of acetylcholine from the Auerbach plexus of the guinea-pig ileum.

The effect of protoveratrine A and germine-3-acetate (GMA) on the release mechanism of acetylcholine from the nerve terminals of the Auerbach plexus in the longitudinal muscle layer of the guinea-pig ileum was studied. Protoveratrine A, GMA and germine potentiated neuroeffector transmission in Auerbach's plexus in the longitudinal muscle preparation provided the neurons were stimulated at low frequencies (less than 10 Hz). Protoveratrine A and GMA enhanced the release of acetylcholine from the nerve terminals during the resting period and at low frequency of stimulation (less than 10 Hz). At continous stimulation with high frequency they were ineffective (greater than 10 Hz). When trains of 20 stimuli, with a pulse interval of 0.1 s (10 Hz) were repeatedly applied with intervals of 0.1 to 20 s between trains, the effect of GMA to increase ACh release depended on the length of the train interval; the longer the resting period between trains the higher was the output of ACh. This fact indicates that the release of ACh increased primarily during the resting periods following single stimuli or trains. The effect of GMA on ACh release proved to be highly temperature-dependent: in the presence of GMA Q10 increasing from 3.25 to 4.92. A high Ca concentration, removal of Mg or lowering of the Na concentration abolished the effect of GMA to enhance ACh release.