Carbonic anhydrase and cardiac ph regulation.
Vandenberg, Jamie I., Nicholas D. Carter, Hugh W. L. Bethell, Antal
Nogradi, Yvonne Ridderstr[angstrom]ale, James C. Metcalfe, and Andrew
A. Grace.
Department of Biochemistry, University of Cambridge, Cambridge CB2
1QW, UK
APStracts 3:0215C, 1996.
Membrane-bound carbonic anhydrase has recently been identified in
mammalian cardiac tissue. In this study we have investigated the
histochemical location and functional role of carbonic anhydrase, CA,
in the ferret heart. Heart sections stained using a modified
Hansson's technique showed CA to be located on capillary endothelial
membranes as well as on sarcolemmal membranes. In the Langendorff
-perfused heart washout of CO2 brought about by switching perfusion
between 25 mM HCO3- /5% CO2 buffered solution and nominally HCO3
-/CO2-free solution caused a transient rise in intracellular pH, pHi,
as measured by the chemical shift of 2-deoxy-glucose-6-phosphate
using 31P NMR spectroscopy. The initial rate of change of pHi,
measured over the first 60-75 seconds of CO2 efflux, was
significantly reduced from 0.41 +/- 0.03 pH units min-1 (n=9) in
control hearts to 0.28 +/- 0.02 pH units min-1 (n=5) in the presence
of the membrane-permeable CA inhibitor 6-ethoxzolamide (p<0.05
compared to control) and to 0.22 +/- 0.04 pH units min-1 (n=5) in the
presence of the membrane-impermeable CA inhibitor CL-11,366
(p<0.01 compared to control). After reperfusion of the ischemic
myocardium both CA inhibitors caused a significant slowing of initial
dpHi/dt (and the initial rate of recovery of contractile function)
compared to control hearts. These results suggest that CA, by
facilitating the hydration/dehydration of CO2/H2CO3, alters the
relative concentrations of CO2 inside and outside the cells such that
it enhances the rate of CO2 transfer from the intracellular to
extracellular compartments and this contributes significantly to pHi
recovery following reperfusion of the ischemic myocardium.
Received 27 November 1995; accepted in final form 18 June 19960
APS Manuscript Number C707-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996