Propranolol regulates cardiac transient outward potassium channel in rat myocardium via cAMP/PKA after short-term but not after long-term ischemia

  • Li Zhang
  • Chao-Qian Xu
  • Yuan Hong
  • Jia-Lin Zhang
  • Ying Liu
  • Mei Zhao
  • Yan-Xiu Cao
  • Yan-Jie Lu
  • Bao-Feng Yang
  • Hong-Li Shan
ORIGINAL ARTICLE
First Online:
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Accepted:

Abstract

It was recently suggested that the antiarrhythmic effect of propranolol, a ß-adrenoceptor antagonist, on ischemic myocardium includes restoration of IK1 current and Cx43 conductance; however, little is known whether effects on the transient outward current Ito contribute. A model of myocardial infarction (MI) by ligating the left anterior descending coronary artery was established. Propranolol was given 1 h or daily for 3 months, whole-cell patch-clamp techniques were used to measure Ito. Kv4.2 and PKA levels were analyzed by Western blot and cAMP level was determined by radioimmunoassay. The results showed that propranolol decreased the incidence of arrhythmias induced by acute ischemia and mortality in 3 month MI rats. Propranolol restored the diminished Ito density and Kv4.2 protein in MI hearts. In addition, neonatal cardiomyocyte pretreatment with propranolol or administrated after hypoxia can resume Ito density. cAMP/PKA was enhanced in acute MI, the reason of decreased Kv4.2 expression. Treatment with propranolol prevented the increased cAMP/PKA in 1 h MI, whereas propranolol had little effect on decreased cAMP/PKA in 3 months MI. This study demonstrated that both short- and long-term propranolol administrations protect cardiomyocytes against arrhythmias and mortality caused by cardiac ischemia; the involvement of cAMP/PKA signal pathway in the regulation of propranolol on Ito acted differently along with the ischemic progression.

Keywords

Myocardial infarction Transient outward potassium current Propranolol cAMP/PKA Kv4.2 

Abbreviations

cAMP

cyclic adenosine monophosphate

PKA

cAMP-dependent protein kinase A

MI

myocardial infarction

Ito

transient outward K+ current

APD

action potential duration

LAD

left anterior descending coronary arteries

EADs

early after-depolarizations

GAPDH

glyceraldehyde phosphate dehydrogenase

HEPES

hydroxyethyl piperazine ethanesulfonic acid

EGTA

egtazic acid

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Notes

Acknowledgements

This work was supported partially by National Basic Research Program of China (973 Program) 2007CB512000 (2007CB512006) to B.Y., the Science Foundation of Ministry of Education of China (207031), and the Scientific Research Foundation for the Returned Overseas Chinese Scholars of Heilongjiang Province of China (LC07C10) to H.S.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Li Zhang
    • 1
  • Chao-Qian Xu
    • 1
  • Yuan Hong
    • 1
  • Jia-Lin Zhang
    • 1
  • Ying Liu
    • 1
  • Mei Zhao
    • 1
  • Yan-Xiu Cao
    • 1
  • Yan-Jie Lu
    • 1
    • 2
  • Bao-Feng Yang
    • 1
    • 2
  • Hong-Li Shan
    • 1
    • 2
    • 3
  1. 1.Department of Pharmacology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of ChinaHarbin Medical UniversityHarbinPeople’s Republic of China
  2. 2.Cardiovascular Research InstituteHarbin Medical UniversityHarbinPeople’s Republic of China
  3. 3.Department of PharmacologyHarbin Medical UniversityHarbinPeople’s Republic of China

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