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Science 14 February 1992:
Vol. 255. no. 5046, pp. 850 - 853
DOI: 10.1126/science.1311127
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Articles

Science, Vol 255, Issue 5046, 850-853
Copyright © 1992 by American Association for the Advancement of Science

articles

Gating of the cardiac Ca2+ release channel: the role of Na+ current and Na(+)-Ca2+ exchange

JS Sham, L Cleemann, and M Morad

Department of Physiology, University of Pennsylvania, Philadelphia 19104.

In cardiac myocytes, calcium influx through the calcium channel is the primary pathway for triggering calcium release. Recently it has been suggested that the calcium-induced calcium release mechanism can also be activated indirectly by the sodium current, which elevates the sodium concentration under the cell membrane, thereby favoring the entry of "trigger" calcium via the sodium-calcium exchanger. To test this hypothesis, sodium current was suppressed by reducing the external sodium concentration or applying tetrodotoxin. At potentials positive to -30 millivolts, calcium release was unaffected. A small calcium release at more negative potentials could be attributed to partial activation of calcium channels, because it was unaltered by replacement of sodium with lithium and was blocked by cadmium. Thus, sodium influx or its accumulation does not initiate calcium release. In addition, sodium-calcium exchange-related calcium release at potentials positive to +80 millivolts has slower kinetics than calcium channel-induced release. Therefore, only the calcium channel gates the fast release of calcium from the sarcoplasmic reticulum in the range of the action potential.


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