Methoxamine inhibits transient outward potassium current through α1A-adrenoceptors in rat ventricular myocytes

alpha(1)-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 (tau(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 alpha(1A)-antagonist 5-methylurapidil but not by the irreversible alpha(1B)-antagonist chloroethylclonidine. These data indicate that stimulation of alpha(1A)-adrenoceptor subtype is involved in the methoxamine-induced reduction of I-to in rat ventricular myocytes.