Decrease in the transmembrane sodium activity gradient in ferret papillary muscle as a prerequisite to the calcium paradox.
Sodium-dependent calcium exchange may be an important mediator of calcium reperfusion damage during the calcium paradox phenomenon. We measured intracellular sodium activity with ion-selective electrodes during a 15-min period of calcium reperfusion in isolated ferret papillary muscles. During the calcium-free period, alpha Nai increased from 9.0 +/- 0.9 to 18.9 +/- 4.3 mM. With reinstitution of calcium there was a significant contracture. The amount of contracture after calcium reinstitution was related to sodium loading during the calcium-free period. We were unable to block sodium entry during the calcium-free period with either nitrendipine, tetrodotoxin, or low concentrations of amiloride. 10(-3) M amiloride or lithium for sodium substitution in the calcium-free period, however, obliterated the increase in alpha Nai activity and the subsequent paradox. These data suggest that sodium loading is a necessary prerequisite for the calcium paradox and that one mechanism of sodium entry is through Na+/Ca2+ exchange. Under these conditions, no increase in the rest force is seen without previous sodium gains, suggesting that sodium-dependent calcium exchange is an important trigger for the calcium reflow, the calcium paradox.
Guarnieri
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Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism*; D005289:Ferrets; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials; D009119:Muscle Contraction; D009568:Nitrendipine / Q000494:pharmacology; D009924:Organ Culture Techniques; D010210:Papillary Muscles / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D007473:Ion Channels; D013779:Tetrodotoxin; D000584:Amiloride; D009568:Nitrendipine; D012964:Sodium; D002118:Calcium