Adrenergic regulation of the rapid component of delayed rectifier K+ currents in guinea pig cardiomyocytes.

ABSTRACT

BACKGROUND: Guinea pig ventricular cardiomyocytes display the rapid component of the delayed rectifier potassium current (Ikr) that contributes to ventricular repolarization and promotes stress-induced arrhythmias. Adrenergic stimulation favors ventricular arrhythmogenesis but its effects on Ikr are poorly understood. METHODS: Adrenergic modulation of Ikr was studied in isolated guinea pig ventricular cardiomyocytes using whole-cell patch clamping. RESULTS: We found that the Ikr amplitude was reduced to 0.66±0.02 and 0.62±0.03 in response to 0.1 µM phenylephrine (PE), an α1AR agonist, and 10 µM isoproterenol (ISO), a ßAR agonist, respectively. The effect of PE can be blocked by the selective α1A-adrenoceptor antagonist 5-methylurapidil, but not by the α1B-adrenoceptor antagonist chloroethylclonidine or α1D-adrenoceptor antagonist BMY7378. Additionally, the effect of ISO can be blocked by the ß1-selective AR antagonist CGP-20712A, but not by the ß2-selective AR antagonist ICI-118551. Although PE and ISO was continuously added to cells, ISO did not decrease the current to a greater extent when cells were first given PE. In addition, PE's effect on Ikr was suppressed by ß1AR stimulation. CONCLUSIONS: Ikr can by regulated by both the α1 and ß ARs system, and that in addition to direct regulation by each receptor system, crosstalk may exist between the two systems.