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 βAR 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 β1-selective AR antagonist CGP-20712A, but not by the β2-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 β1AR stimulation. CONCLUSIONS: Ikr can by regulated by both the α1 and β ARs system, and that in addition to direct regulation by each receptor system, crosstalk may exist between the two systems.
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 βAR 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 β1-selective AR antagonist CGP-20712A, but not by the β2-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 β1AR stimulation. CONCLUSIONS: Ikr can by regulated by both the α1 and β ARs system, and that in addition to direct regulation by each receptor system, crosstalk may exist between the two systems.
Entities:
Keywords:
Adrenergic receptors (ARs); cardiomyocytes; crosstalk; potassium current
Authors: Christoph A Karle; Edgar Zitron; Wei Zhang; Sven Kathöfer; Wolfgang Schoels; Johann Kiehn Journal: Cardiovasc Res Date: 2002-02-01 Impact factor: 10.787
Authors: Brian C Jensen; Philip M Swigart; Teresa De Marco; Charles Hoopes; Paul C Simpson Journal: Circ Heart Fail Date: 2009-08-06 Impact factor: 8.790