Methoxamine inhibits transient outward potassium current through alpha1A-adrenoceptors in rat ventricular myocytes.
alpha1-Adrenoceptor agonists are known to reduce transient outward potassium current (I(to)) in the heart. The aim of this study was to analyze the effect of methoxamine (mtx) on I(to) and to elucidate which adrenoceptor subtype was involved in this effect. We used the whole-cell configuration of the patch-clamp technique to record I(to). Our experiments confirm that mtx induces a dose-dependent decrease of I(to) that is characterized by an acceleration of time to peak (3.5 +/- 0.2 and 2.3 +/- 0.3 ms for control and mtx, respectively), and a decrease in both inactivation time constants (T(fast) was reduced from 20.8 +/-2.6 to 14.9 +/- 1.1 ms, and tau(slow) was reduced from 138 +/- 32.1 to 114 +/- 28.7 ms; n = 7). All these effects were antagonized by prazosin and the alpha1A-antagonist 5-methylurapidil but not by the irreversible alpha1B-antagonist chloroethylclonidine. These data indicate that stimulation of alpha1A-adrenoceptor subtype is involved in the methoxamine-induced reduction of I(to) in rat ventricular myocytes.
Martínez
M L
ML
Institute of Pharmacology and Toxicology (CSIC-UCM), Universidad Complutense, Madrid, Spain.
Delgado
C
C
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008729:Methoxamine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; C051731:chlorethylclonidine; D008729:Methoxamine; D003000:Clonidine; D011188:Potassium; D011224:Prazosin