Man Si1, Jiaxi Xu, Fan Zhang, Chuan Wang, Xiaona Du, Hailin Zhang. 1. Key Laboratory of Neural and Vascular Biology, Ministry of Education, Key Laboratory of New Drug Pharmacology and Toxicology, Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
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.
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.