Regulation and deregulation of cardiac na+–ca2+ exchange in giant excised sarcolemmal membrane patches

ABSTRACT A PLASMALEMMAL Na+–Ca2+ exchange mechanism1,2 is an important electrogenic determinant of contractility in cardiac cells3–5. As in other cell types6–8, calcium influx by

Na+–Ca2+" exchange is secondarily activated by cytoplasmic calcium4 and probably ATP9, but these modulatory mechanisms are either absent or altered in isolated cardiac sarcolemmal

vesicles5,12. Involvement of a calcium-dependent protein kinase in exchange regulation has been suggested7,10 but not verified5,11. Here I describe measurements of outward Na+–Ca2+ exchange

current, corresponding to calcium influx, in giant excised sarcolemmal Patches11 from guinea pig myocytes. The exchange current is stimulated by both calcium and Mg–ATP from the cytoplasmic

face, evidently through separate mechanisms. Activation by cytoplasmic calcium takes place within seconds, is reversible, and does not require ATP. Stimulation by Mg–ATP reverses only slowly

over > 10 min, or not at all. Unexpectedly, a substantial decrease in exchange current occurs during activation by cytoplasmic sodium, which seems to reflect an inactivation process

rather than ion concentration changes or a 'first pass' exchange cycle. This apparent inactivation, and the modulations by cytoplasmic calcium and Mg–ATP, are all abolished by

brief treatment of the cytoplasmic surface with chymotrypsin, leaving the exchanger in a maintained state of high activity. Therefore, limited proteolysis deregulates Na+–Ca2+ exchange and

could contribute to the loss of secondary regulation of the exchange in isolated sarcolemmal vesicles. Access through your institution Buy or subscribe This is a preview of subscription

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ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS SARCOPLASMIC RETICULAR CA2+-ATPASE

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University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, 75235, USA Donald W. Hilgemann Authors * Donald W. Hilgemann View author publications You can also search for this

author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Hilgemann, D. Regulation and deregulation of cardiac Na+–Ca2+ exchange in

giant excised sarcolemmal membrane patches. _Nature_ 344, 242–245 (1990). https://doi.org/10.1038/344242a0 Download citation * Received: 31 July 1989 * Accepted: 12 January 1990 * Issue

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