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    
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.
Na Li; Nan Jia; De-Zai Dai; Chen Hu; Yin Dai
Related Documents :
11447308 - Endothelin and heart failure.
1988658 - A comparison of the hemodynamic effects of endothelin-1 and sarafotoxin s6b in consciou...
19479828 - Improved endothelial function after endothelin receptor blockade in patients with syste...
11811378 - The endothelin-aldosterone axis and cardiovascular diseases.
3090368 - Stimulation of the scavenger receptor on monocytes-macrophages evokes release of arachi...
8278048 - Expression of multiple alpha adrenergic receptor subtype messenger rnas in the adult ra...
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:  -    
Research Division of Pharmacology, China Pharmaceutical University, Nanjing, 210009, China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Involvement of Nonselective Cation Channels in the Depolarisation Initiating Vasomotion.