Modulation of hormone-induced calcium oscillations by intracellular pH in rat hepatocytes.
Single isolated rat hepatocytes were used to investigate the influence of intracellular pH (pHi) on hormone-induced cytosolic Ca2+ oscillations, using videofluorescence microscopy. Although pHi did not vary after alpha-adrenergic stimulation, manipulations of pHi induced pronounced alterations in the frequency of oscillations. Increasing the resting pHi with ammonium chloride (5-20 mM), trimethylammonium (2-10 mM), or triethylammonium (1.2-8 mM) reduced the frequency of oscillations. A change in pHi of > 0.25 was sufficient to reversibly inhibit oscillations. This effect could be overcome by increasing the agonist concentration or by adding 8-bromoadenosine 3',5'-cyclic monophosphate, an agent known to potentiate the alpha-adrenergic response. Cellular acidification, obtained by the ammonium prepulse method as well as by application of acetate or the ionophore nigericin, in the continuous presence of agonist was accompanied by a modest frequency increase of the oscillations, leading in some cases to an overstimulated state. This study indicates that pHi, within a range of values expected to occur in vivo (0.1-0.2 pH units), exerts a chronotropic effect on phenylephrine-induced Ca2+ oscillations. In contrast, oscillations induced by ADP or vasopressin were pHi invariant.
Chatton
J Y
JY
Institute of Pharmacology, University of Bern, Switzerland.
Liu
H
H
Stucki
J W
JW
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000468:Alkalies / Q000378:metabolism; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006728:Hormones / Q000494:pharmacology*; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009991:Oscillometry; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000316:Adrenergic alpha-Agonists; D000468:Alkalies; D006728:Hormones; D000643:Ammonium Chloride; D010656:Phenylephrine; D006859:Hydrogen; D002118:Calcium