Document Detail


Propranolol regulates cardiac transient outward potassium channel in rat myocardium via cAMP/PKA after short-term but not after long-term ischemia.
MedLine Citation:
PMID:  20499050     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
It was recently suggested that the antiarrhythmic effect of propranolol, a ss-adrenoceptor antagonist, on ischemic myocardium includes restoration of I(K1) current and Cx43 conductance; however, little is known whether effects on the transient outward current I(to) 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 I(to). 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 I(to) density and Kv4.2 protein in MI hearts. In addition, neonatal cardiomyocyte pretreatment with propranolol or administrated after hypoxia can resume I(to) 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 I(to) acted differently along with the ischemic progression.
Authors:
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
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-25
Journal Detail:
Title:  Naunyn-Schmiedeberg's archives of pharmacology     Volume:  382     ISSN:  1432-1912     ISO Abbreviation:  Naunyn Schmiedebergs Arch. Pharmacol.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-22     Completed Date:  2010-09-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0326264     Medline TA:  Naunyn Schmiedebergs Arch Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  63-71     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Antagonists / administration & dosage,  pharmacology*
Animals
Blotting, Western
Cyclic AMP / metabolism
Cyclic AMP-Dependent Protein Kinases / metabolism
Disease Models, Animal
Drug Administration Schedule
Male
Myocardial Infarction / drug therapy,  physiopathology
Myocardial Ischemia / drug therapy,  physiopathology
Myocytes, Cardiac / drug effects,  metabolism
Patch-Clamp Techniques
Propranolol / administration & dosage,  pharmacology*
Rats
Rats, Wistar
Shal Potassium Channels / drug effects*,  metabolism
Time Factors
Chemical
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Shal Potassium Channels; 525-66-6/Propranolol; 60-92-4/Cyclic AMP; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases

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