Regulation and deregulation of cardiac Na(+)-Ca2+ exchange in giant excised sarcolemmal membrane patches.

Abstract:

:A plasmalemmal Na(+)-Ca2+ exchange mechanism is an important electrogenic determinant of contractility in cardiac cells. As in other cell types, calcium influx by Na(+)-Ca2+ exchange is secondarily activated by cytoplasmic calcium and probably ATP, but these modulatory mechanisms are either absent or altered in isolated cardiac sarcolemmal vesicles. Involvement of a calcium-dependent protein kinase in exchange regulation has been suggested but not verified. Here I describe measurements of outward Na(+)-Ca2+ exchange current, corresponding to calcium influx, in giant excised sarcolemmal patches 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 greater than 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.

journal_name

Nature

journal_title

Nature

authors

Hilgemann DW

doi

10.1038/344242a0

subject

Has Abstract

pub_date

1990-03-15 00:00:00

pages

242-5

issue

6263

eissn

0028-0836

issn

1476-4687

journal_volume

344

pub_type

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