Circulation Research, Vol 55, 227-237, Copyright © 1984 by American Heart Association

ARTICLES

Calcium, sodium, and the calcium paradox

WG Nayler, SE Perry, JS Elz and MJ Daly

The effect of "sodium loading," of verapamil and of nifedipine on the gain in calcium and sodium, and on the loss of myoglobin, during the calcium paradox in adult rat hearts was examined. Raising cell sodium from 56.5 +/- 2.6 to 129.5 +/- 10.2 mumol sodium/gram dry weight did not alter the degree or rate of calcium gain or myoglobin release during calcium repletion after long periods (greater than 2 minutes) of calcium-free perfusion; under these conditions, and in the presence of 10 micrograms/liter verapamil, calcium gain was enhanced. However, after shorter periods (0.5-1.5 minutes), of calcium-free perfusion, calcium gain was enhanced in "sodium-loaded" hearts, even in the absence of verapamil, and particularly during the early stages of repletion. The presence of 1 and 10 mumol/liter dl-verapamil and 1 mumol/liter nifedipine before, during, and after 10 minutes of calcium- free perfusion significantly (P less than 0.01) slowed the early (up to 1 minute for verapamil and 2 minutes for nifedipine) but not the late gain in calcium. When verapamil was present, the late gain in calcium was actually enhanced. These agents also abolished the early (45 seconds) but not the late (greater than 2 minutes) gain in sodium that occurs during repletion. We propose that the gain in calcium that occurs during calcium repletion after a period of calcium-free perfusion can be divided into at least two phases (early and late), and that the early phase contains a verapamil/nifedipine-sensitive component and a verapamil/nifedipine-insensitive component, the latter probably involving sodium-calcium exchange.

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