Modulation of hormone-induced calcium oscillations by intracellular
ph in rat hepatocytes.
Chatton, Jean-Yves, Haiyan Liu, and J[diaeresis]org W. Stucki.
Institute of Pharmacology, University of Berne,
Friedb[umlaut]uhlstrasse 49, CH-3010 Berne - Switzerland
APStracts 3:0253G, 1996.
Single isolated rat hepatocytes were used to investigate the influence
of intracellular pH (pHi) on hormone-induced cytosolic Ca2&
oscillations using video-fluorescence microscopy. While pHi did not
vary following [alpha]-adrenergic stimulation, manipulations of pHi
induced pronounced alterations of the frequency of oscillations.
Increasing the resting pHi using ammonium chloride (5-20 mM),
trimethylammonium (2-10 mM) or triethylammonium (1.2-8 mM) reduced
the frequency of oscillations. A DpHi >&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
pre-pulse 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 over-stimulated 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.
Received 24 June 1996; accepted in final form 25 October 1996.
APS Manuscript Number G251-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996