Document Detail


Role of endothelin in the effects of isoprenaline on potassium currents and calsequestrin 2 expression in the heart.
MedLine Citation:
PMID:  20039908     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
SUMMARY 1. Activation of beta-receptors may modulate potassium channels and calcium handling proteins AND serve as a basis for arrhythmogenesis. We determined whether an endothelin (ET) receptor antagonist CPU0213 could relieve the ISO (isoprenaline) induced changes in I(Kr) and I(Ks) and calsequestrin 2 (CASQ2) in the heart. 2. In isolated ventricular myocytes the I(Kr) and I(Ks) currents and expression for CASQ2, FKBP12.6, SERCA2a and ET(A)R were measured in the presence of ISO and either propranolol or CPU0213. 3. In the presence of ISO, I(Kr) and I(Ks) currents were significantly exaggerated and FKBP12.6, SERCA2a and CASQ2 were downregulated together with upregulation of ET(A)R in the myocardium. Interestingly, endothelin-1 was also effective to downregulate the expression of CASQ2. These changes were partially relieved by either CPU0213 or propranolol. 4. I(Kr) and I(Ks) currents can be separated into the exaggerated/induced and basic component in the presence of ISO. The former, induced by ISO, is pathological, sensitive to either CPU0213 or propranolol. 5. Exaggerated I(Kr) and I(Ks) and downregulated CASQ2 by ISO are relevant to stress related events in which the ET pathway is actively involved. By suppressing the ISO-exaggerated I(Kr) and I(Ks), and normalizing expression of CASQ2 endothelin receptor antagonism is likely promising in dealing with stress related cardiac arrhythmias.
Authors:
Na Li; Nan Jia; De-Zai Dai; Chen Hu; Yin Dai
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2009-12-23
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  -     ISSN:  1440-1681     ISO Abbreviation:  -     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-12-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Research Division of Pharmacology, China Pharmaceutical University, Nanjing, 210009, China.
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