Transmembrane mechano-chemical coupling in cardiac myocytes: novel
activation of gi by hypo-osmotic swelling.
Hilal-Dandan, Randa, and Laurence L. Brunton.
Departments of Pharmacology and Medicine, University of California,
San Diego
APStracts 2:0102H, 1995.
We have studied the effect of hypo-osmotic swelling on cAMP metabolism
in isolated cardiac myocytes. Decreasing extracellular osmolarity by
12.5 to 50% results in graded inhibition (10-40%) of isoproterenol
-stimulated and forskolin-stimulated cAMP accumulation but does not
affect basal and hormone-stimulated phosphoinositide hydrolysis or
cellular ATP content. Treatment with pertussis toxin does not alter
the swelling response but abolishes the inhibitory effect of swelling
on cAMP accumulation. The response to swelling seems not to involve
the release of effectors known to couple to Gi in myocytes: BQ-123,
atropine and adenosine deaminase do not alter the inhibitory effect
of swelling on isoproterenol-stimulated cAMP accumulation;
conditioned medium from swollen cells, with restored osmolarity, has
no effect on cAMP accumulation when added to control myocytes. In
distinction to these effects on myocytes, swelling enhances hormone
-stimulated cAMP accumulation in cultured S49 lymphoma cells. We
conclude that swelling of cardiac myocytes inhibits cAMP accumulation
through a mechanism that involves activation of a pertussis toxin
-sensitive Gi protein. Activation of Gi by this means may contribute
to adrenergic hyporesponsiveness in hypoxic and ischemic myocardium.
Received 14 November 1994; accepted in final form 3 March 1995.
APS Manuscript Number H1019-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 4 April 1995.