Role of adenosine-triphosphate-sensitive potassium channels in the mechanical responses of agonist-stimulated isolated porcine coronary arteries.
The aim of this study was to provide evidence supporting the hypothesis that the reactivity of the vascular smooth muscle (VSM) cell is controlled at the cell membrane level by adenosine triphosphate (ATP)-sensitive (KATP) K channels, acting as signal amplifying modulators of the function of L-type voltage operated Ca channels. KATP channels, detected in numerous parts of the vascular tree, are targets for extracellular ATP or adenosine, which stimulate A2 receptors mediating relaxation. To test the hypothesis of a putative role for KATP channels switching between vasoconstricting and vasodilating mechanisms, changes in contractile reactivity were measured in helical strips of epicardial porcine coronary artery preparations in response to various vasoconstrictor and vasodilator substances or combination of these. The data show that the tonic component of the biphasic contractions induced by several agonists (acetylcholine, histamine, serotonin), as well as the contractions induced by F- ions (2 mmol/l), which activate G proteins downstream of the receptors could be inhibited by both adenine nucleotides and by cromakalim, known as openers of KATP channels. The EC50 values for the dose-response curves established for the inhibition of histamine-induced contractions by adenosine were nearly identical to those obtained for the relaxations of fluoride-induced contractions by cromakalim: resp. 0.556 +/- 0.081 and 0.590 +/- 0.052 mumol/l (n = 6). Contractions induced by BAY k 8644 (20 nmol/l), by tetraethylammonium (5 mmol/l) or by beta-methyldigoxin (1 mumol/l) were also strongly inhibited by 1 mumol/l cromakalim. From the results obtained in this study, it may be concluded that KATP channels could possibly play an integrative role in the signal transduction mechanism in VSM in that they act as common effectors for both vasoconstrictor and vasodilator agonists.
Nguyen
D H
DH
Abteilung für Allgemeine Physiologie, Universität Ulm, Germany.
D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D019806:Cromakalim / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D007501:Iron / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D015221:Potassium Channels; D014665:Vasodilator Agents; D019806:Cromakalim; D000255:Adenosine Triphosphate; D007501:Iron; D019204:GTP-Binding Proteins; D000241:Adenosine; D011188:Potassium