Further studies on Nivalin P-induced changes in muscle fiber membrane processes

Nivalin P, composed of Nivalin (galanthamine hydrobromide) and Pymadin (4-aminopyridine hydrochloride), was applied extracellularly to isolated skeletal muscle fibers during prolonged activity (fatiguing) to better understand the effects of the drug on membrane ionic processes. Changes in intracellular action potential (ICAP) and twitch (Tw) parameters were monitored from treated and untreated fibers during uninterrupted activity (endurance time, ET) produced by repetitive stimulation every 200 msec for 3 min. Nivalin P-induced a shortening of the ET, drastic changes in repolarization of the ICAP corresponding to changes in negative afterpotential and falling area and an initial increase of the Tw amplitude and duration. These results suggest that Nivalin P: (i) inhibits the Na+, K(+)-pump due to nonspecific reduction of Na+ influx, stimulates the Na(+)-Ca2+ exchanger and inhibits K+ conductance; (ii) increases Ca2+ release and delays Ca2+ uptake under sufficient depolarization. It was concluded that fatigue develops faster in the presence of Nivalin P.