Calcium-mediated intracellular acidification and activation of Na(+)-H+ exchange in adrenal glomerulosa cells stimulated with potassium.
Intracellular pH (pHi) regulation by Na(+)-H+ exchange is important in cellular responses to hormones and growth factors, particularly those which raise cytosolic Ca2+ (Cai). Since elevation of Cai occurs when adrenal glomerulosa cells are stimulated by angiotensin II (Ang II) and high external K+ (Ko), we evaluated the relationship of Na(+)-H+ exchange to calcium movement particularly during high Ko stimulation of bovine glomerulosa cells. Inhibition of Na(+)-H+ exchange by dimethylamiloride markedly reduced aldosterone secretion in response to 8 mM Ko. This high Ko stimulation was accompanied by a rise in dimethylamiloride-sensitive Na+ influx and pHi acidification which was extracellular Ca2+ (Cao) dependent. High Ko also produced a rise in Ca2+ influx, Cai levels and Ca2+ efflux at 37 C. However, at 4 C, Ca2+ influx remained intact, but Ca2+ efflux and cellular acidification were inhibited. In contrast, Ang II produced protein kinase C (PKC) activation accompanied by a Na(+)-H+ exchange-dependent rise in pHi which was independent of Cao. After PKC depletion by phorbol ester pretreatment, Ang II also produced a Cao-dependent cell acidification as with high Ko. Thus, Na(+)-H+ exchange is activated by both Ang II and high Ko but by different mechanisms. High Ko stimulation induces an enhanced cellular acidification, whereas Ang II induces alkalinization driven by PKC activation of the antiporter. These findings suggest that a physiological role of Na(+)-H+ exchange may be, in part, to counteract the acidification produced by enhanced active Ca2+ efflux (via Ca2+ pumping) during both high Ko and Ang II stimulation of aldosterone secretion.
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
P R
PR
Conlin
M
M
Cirillo
G
G
Zerbini
G H
GH
Williams
M L
ML
Canessa
D000450:Aldosterone / Q000378:metabolism; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008954:Models, Biological; D011188:Potassium / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers; D015384:Zona Glomerulosa / Q000187:drug effects / Q000378:metabolism*
D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; D000804:Angiotensin II; C039465:5-dimethylamiloride; D000450:Aldosterone; D000584:Amiloride; D012964:Sodium; D011188:Potassium; D002118:Calcium