Effect of Caffeine on Calcium Flux across the Sarcolemma of Guinea Pig Atrial Trabeculae during Contracture

ABSTRACT

The changes in extracellular calcium activities during contractures of guinea pig atrial trabecular muscles were measured with Ca2+-selective electrodes. When the tissue was superfused with Na+-free Tyrode solution extracellular Ca2+ activities were decreased and contractures were induced with some delay. When the contracture was relaxed with Na+-containing Tyrode solution, extracellular Ca2+ activities were increased transiently and recovered in a Na+-dependent manner. The magnitude of extracellular Ca2+ activity decreased was proportional to the maximum magnitude of contracture induced by Na+-free solution. Addition of caffeine (10 mM) to Na+-free solution induced transient contracture following slow development of contracture and an increase in extracellular Ca2+ activity. Removal of caffeine from Na+-free solution caused a slow relaxation of contracture and a decrease in extracellular Ca2+ activity. These results confirm that caffeine blocks Ca2+ uptake by the sarcoplasmic reticulum (SR) resulting in an increase in sarcoplasmic Ca2+ activity. Ca2+ activity in the extracellular space, the amount of Ca2+ transported into the cell(Ca2+ depletion in the extracellular space), and the magnitude of contracture are well correlated. Present experiments suggest that extracellular use of Ca2+-selective electrodes provides continuous and quantitative monitoring of Na+-dependent Ca2+ flux across the cardiac cell membrane.