Involvement of protein kinase A and C in norepinephrine- and angiotensin II-induced modulation of cardiac IKs

Abstract

Background/aims: The slow component of the delayed rectifier K(+) current (IKs) is one of the major repolarizing currents in the heart. Yet, the signaling mechanisms for norepinephrine- and angiotensin II-induced modulation of IKs in cardiac myocytes are far from being well understood.

Methods: The whole-cell patch clamp technique was used to study the effects of norepinephrine and angiotensin II on IKs in guinea pig cardiac myocytes.

Results: Both the α1- and β-adrenoceptor inhibitors attenuated norepinephrine-induced enhancement of IKs, which was also significantly depressed by inhibitors of protein kinase A and C. Angiotensin II-induced inhibition of the IKs was inhibited by angiotensin type 1 receptor blocker losartan and protein kinase C inhibitor.

Conclusions: Norepinephrine and angiotensin II modulated IKs with opposite effects and distinct mechanisms. The activation of protein kinase A was the major component of the norepinephrine-induced activation of IKs while the activation of protein kinase C was responsible for the angiotensin II-induced inhibition of IKs. There was crosstalk between the α1- and β-adrenoceptor that also contributed to the norepinephrine-induced enhancement of IKs. This current study provides new insight into the cellular signaling mechanisms of norepinephrine and angiotensin II, the two important modulators of cardiovascular function.