Ca (++) -dependence of caffeine modulation of the rate-force relation in canine cardiac Purkinje fibers
Satoh, H.; Vassalle, M.
Journal of Pharmacology and Experimental Therapeutics 278(2): 826-835
1996
ISSN/ISBN: 0022-3565 PMID: 8768737 Document Number: 463587
The effects of caffeine on rate-force relation and their Ca++ dependence were studied in canine cardiac Purkinje fibers. At constant rate, caffeine increased and then decreased force. During drives at different rates (15, 60 and 120/min), 1 mM caffeine caused the largest positive inotropic effect at the slowest rate, but in 8.1 mM (Ca++)-o caffeine no longer increased force even at 15/min. Interruptions of drive were followed by a positive and then a negative staircase: caffeine (1-4 mM) blunted these effects. A sudden decrease in rate caused a positive staircase: caffeine decreased and caffeine plus 8.1 mM (Ca++)-o abolished it. A sudden increase in rate caused a negative staircase and on recovery a positive staircase: caffeine reduced and caffeine plus 8.1 mM (Ca++)-o could reverse them. In low (Ca++)-o (0.54 mM), caffeine caused only a positive inotropic effect and did not modify the rate-force relation patterns. High (Ca++)-o ( gt 8.1 mM) reversed the staircase patterns induced by a rate increase; adding caffeine shifted the reversal to lower (Ca++)-o. Low (Na)-o altered the rate-force relation similarly to high (Ca++)-o, and caffeine exaggerated its effects. Decreasing (Ca++)-i by means of tetrodotoxin or high (K+)-o antagonized the caffeine effects on the rate-force relation. We conclude that caffeine markedly modulates the rate-force relation through a Ca++-dependent mechanism. This mechanism appears to involve a supraoptimal increase in (Ca++)-i rather than a decrease in Ca++ released during the action potential.