Alpha-adrenergic modulation of transient outward current in hyperthyroid rabbit myocytes

Abstract

The alpha 1-adrenergic modulation of the transient outward potassium current (I(t)) was studied in single cardiac myocytes obtained from normal (euthyroid) and hyperthyroid rabbits. Rabbits were made hyperthyroid by four or five daily intraperitoneal injections of 0.4 mg/kg body wt thyroxine. Currents were recorded using the whole cell, suction-electrode, voltage-clamp method. It was found that the alpha-adrenergic agonist methoxamine attenuates I(t) in rabbit ventricular cells, as reported earlier for atrial cells. This attenuation is significantly reduced in the hyperthyroid state. For example, 0.2 mM reduces I(t) magnitude (at +20 mV) by close to 40% in euthyroid cells and by only 20% in the hyperthyroid cells. Half-maximal effective concentration values (extrapolated) are close to 0.4 mM in normal and 1 mM in hyperthyroid cells. Preliminary results show similar effects in atrial cells as well. These results may be related to a decrease in the density of membrane alpha-adrenergic receptors in hyperthyroid conditions, or to the induction of a new class of I(t) channels that is less sensitive to alpha-agonists.