Low external ph limits cell death in energy depleted cardiomyocytes
by decreasing ca2+ overload via na+/ca2+ exchange inhibition.
Atsma, Douwe E., E. M. Lars Bastiaanse, Lizet Van Der Valk, Arnoud Van
Der Laarse.
Department of Cardiology, University Hospital, Leiden, The
Netherlands
APStracts 2:0555H, 1995.
We studied the effect of external pH (pHe) on cell injury, ATP
content, intracellular concentration of Ca2+ ([Ca2+]i), Na+ ([Na+]i)
and H+ (pHi) during metabolic inhibition (Mi) (NaCN + 2-deoxyglucose)
in neonatal rat cardiomyocytes. Cell death during Mi decreased at pHe
below 7.4, with practically no cell death at pHe 6.0. Lowering pHe
resulted in only temporary ATP conservation. During Mi at pHe 7.4,
[Ca2+]i rose from 86 +/- 44 nM to 2.5 +/- 0.4 [mu]M, but at pHe 6.0
to only 510 +/- 215 nM. Upon Mi at pHe 7.4, pHi decreased from 7.25
+/- 0.06 to 6.82 +/- 0.16, but at pHe 6.0 to 6.34 +/- 0.17. During Mi
at pHe 7.4, [Na+]i increased from 9.1 +/- 0.86 mM to 26.1 +/- 4.1 mM.
At pHe 6.0, [Na+]i rose more rapidly, to 27.3 +/- 3.5 mM. At
pHe<7.4, sarcolemmal Na+/Ca2+ exchanger activity, involved in
the development of Ca2+ overload, was decreased, as assessed during
Na+-free incubation. We conclude that low pHe protects cardiomyocytes
during Mi by limiting Ca2+ overload via Na+/Ca2+ exchanger
inhibition.
Received 7 June 1995; accepted in final form 16 November 1995.
APS Manuscript Number H521-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 December 95