title: Dependence of Ca2+ channel currents on endogenous and exogenous sources of ATP in portal vein smooth muscle.
abstract: Metabolic pathways in vascular smooth muscles (VSM) appear to be functionally compartmentalized such that glycolysis fuels membrane-related processes, whereas oxidative processes fuel actin-myosin interaction. Because ATP influences Ca2+ channel activity, we examined the effects of ATP and metabolic substrates on Ca2+ channel activity with 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 pipette. Cells perfused with 1, 3, and 5 mMATP 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 rundown. 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 with 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 in 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 with 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.
authors.affiliation: Department of Molecular and Cellular Physiology, University of Cincinnati, Ohio 45267-0576, USA.
authors.forename: J N
authors.initials: JN
authors.lastname: Lorenz
authors.forename: R J
authors.initials: RJ
authors.lastname: Paul
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology* / Q000502:physiology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D003486:Cyanides / Q000494:pharmacology; D004553:Electric Conductivity; D006019:Glycolysis; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009994:Osmolar Concentration; D011169:Portal Vein / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity
chemical_list: D015220:Calcium Channels; D003486:Cyanides; D007461:Iodoacetates; D000255:Adenosine Triphosphate; D019807:Iodoacetic Acid