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.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002595:Cevanes / Q000494:pharmacology*; D004558:Electric Stimulation; D005861:Germine Acetates / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000378:metabolism / Q000648:ultrastructure*; D012508:Sarcolemma / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013268:Stimulation, Chemical; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D002595:Cevanes; D005861:Germine Acetates; D013779:Tetrodotoxin; D012964:Sodium; C013537:germitrine