Twitch potentiation induced by caffeine in the mouse diaphragm depends on external calcium ions in the absence of potassium ions

Abstract

1. 1. Removal of external K + ions increases the amplitude of directly elicited twitch contractions of the mouse diaphragm (Nishimura et al., 1996). This increase depends on external Ca 2+ ions. 2. 2. We examined the effect of caffeine (2 mM) on this increase in twitch amplitude. The mouse diaphragm muscle was directly stimulated in the presence of d-tubocurarine (10 μM). 3. 3. Caffeine increased the amplitude of twitches in a standard bathing solution. This effect was maintained in a solution without either K + or Ca 2+ ions but was abolished in a solution from which both ions were absent. Readdition of Ca 2+ ions restored the potentiating effect of caffeine. 4. 4. In the presence of caffeine, removal of both K + and Ca 2+ ions decreased the resting membrane potentials of muscle fibers to about−53 mV. The readdition of 2 mM Ca 2+ ions restored the membrane potentials. 5. 5. Twitch potentiation in the absence of external K + ions was attenuated by 10 μM bepridil but not by 3 μM verapamil or 10 μM Cd 2+ ions. 6. 6. These results support the hypothesis that Na +-Ca 2+ exchange can support twitch contraction during the inhibition of Na +-K +-ATPase activity. The influx of Ca 2+ ions into the cells might be stored in the sarcoplasmic reticulum.