Modulation effect of β1-adrenergic receptor on rapid component of the delayed rectifier potassium current in ventricular myocytes of chronic heart failure / 中国药理学通报

ABSTRACT

Aim To investigate the effects of β1-ad-renergic receptor (β1-AR ) on rapid component of the delayed rectifier potassium current ( IKr ) in ventricular myocytes of guinea pigs with chronic heart failure ( CHF) . Methods The CHF model of guinea pigs was established by descending thoracic aortic banding . Whole-cell patch-clamp technique was used to record IKr in ventricular myocytes. The effects ofβ1-AR on IKr in CHF ventricular myocytes were detected and its mechanisms were studied by pretreatment with protein kinase A ( PKA ) inhibitor and calmodulin kinase II( CaMK II) inhibitor. Results In CHF ventricular myocytes, xamoterol, the selectiveβ1-AR agonist, de-creased IKr by (52±8)% and prolonged action poten-tial duration. These effects were completely abolished by pretreatment of myocytes with CGP20712A, a selec-tive β1-AR antagonist. íamoterol only decreased IKr by (28±3)% by pretreatment of CHF myocytes with specific PKA inhibitor KT5720 . KN93 , an inhibitor of CaMKII, did not attenuate the inhibitory effect on CHF ventricular myocytes. Conclusion IKr is inhibi-ted by β1-AR activation in CHF ventricular myocytes. PKA, but not CaMKII signaling pathway is involved in, at least in part, the inhibitory effect ofβ1-AR acti-vation on IKr.