title: Involvement of protein kinase A and C in norepinephrine- and angiotensin II-induced modulation of cardiac IKs.
abstract: OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: Man
authors.initials: M
authors.lastname: Si
authors.forename: Jiaxi
authors.initials: J
authors.lastname: Xu
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Chuan
authors.initials: C
authors.lastname: Wang
authors.forename: Xiaona
authors.initials: X
authors.lastname: Du
authors.forename: Hailin
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D051668:Delayed Rectifier Potassium Channels / Q000502:physiology*; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology; D032383:Myocytes, Cardiac / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology
chemical_list: D051668:Delayed Rectifier Potassium Channels; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D000804:Angiotensin II; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D009638:Norepinephrine