Dependence of ca2+ channel currents on endogenous and exogenous
sources of atp in rat portal vein smooth muscle cells.
Lorenz, John N., and Richard J. Paul.
Department of Molecular and Cellular Physiology, University of
Cincinnati, P.O. Box 670576, Cincinnati, OH 45267-0576
APStracts 3:0365H, 1996.
Metabolic pathways in vascular smooth muscle (VSM) appear to be
functionally compartmentalized such that glycolysis fuels membrane
-related processes, whereas oxidative processes fuel actin-myosin
interaction Since ATP has been reported to influence Ca2+ channel
activity, we examined the effects of ATP and metabolic substrates on
Ca2+ channel activity using patch clamp techniques in VSM cells
isolated from rat portal vein. The peak magnitude of the Ca2+ channel
currents was found to depend on the ATP concentration in the patch
pipet. Cells perfused with 1, 3 and 5 mM ATP had mean peak currents
of 4.7 0.6, 12.2 1.9, and 17.6 2.0 pA/pF, respectively, and all
currents showed substantial run-down. In separate experiments
performed in the absence of intracellular ATP, provision of
glycolytic but not oxidative substrates was able to maintain Ca2+
channel currents at levels comparable to those seen in the presence
of 1 mM ATP. In the presence of 5 mM ATP, provision of glycolytic
substrates resulted in a high peak current amplitude that was also
very stable. Finally, metabolic inhibition with cyanide and
iodoacetate caused a significant increase the rate of current
rundown, even in the presence of 5 mM ATP. These findings indicate
that Ca2+ channel current is strongly dependent on ATP and that the
source of ATP can also be an important factor. Compared to exogenous
provision of ATP, endogenous metabolism preferentially maintained
Ca2+ channel currents, consistent with the hypothesis of a
functionally separate subsarcolemmal compartment. This provides an
effective pathway for linking E-C coupling and vascular contractility
to the metabolic state of the vascular cell.
Received 14 December 1995; accepted in final form 19 August 1996.
APS Manuscript Number H1168-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996