Effects of low sodium perfusion on cardiac caffeine sensitivity and calcium uptake

Myocardial compartmentation of calcium was investigated in the arterially perfused rabbit interventricular septum under conditions of augmented calcium uptake. Reduction of perfusate sodium concentration (100-36 mM [Na]0) produced the expected increased active force development and an increased myocardial calcium content that was inversely proportional to [Na]0. Caffeine was used to inhibit calcium uptake by the sarcoplasmic reticulum (SR) and to stimulate SR calcium release. The diastolic tension response to caffeine was also inversely proportional to [Na]0: at [Na]0 of 139 mM, 10 mM caffeine increased diastolic tension by 20%; whereas at 36 mM [Na]0 diastolic tension increased by 205%. The increase in diastolic tension in response to caffeine was considered a reflection of increased cytosolic calcium. The increase in diastolic tension with caffeine required that reduced [Na]0 be present at the time caffeine was administered. Caffeine sensitivity (measured by an increase in diastolic tension) and active force development declined to control levels within 3 minutes after the end of a 40 minute period of low [Na]0 perfusion despite the presence of an additional 1 mmole calcium per kg dry wt in the muscle at the 3 minute mark when caffeine was added. The results indicate that low [Na]0 perfusion induces an increment in myocardial calcium content, a major fraction of which is neither related directly to contractility nor involved in the response to caffeine.