Document Detail


Targeted inactivation of cystic fibrosis transmembrane conductance regulator chloride channel gene prevents ischemic preconditioning in isolated mouse heart.
MedLine Citation:
PMID:  15289377     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Recent evidence suggests that chloride channels may be involved in ischemic preconditioning (IPC). In this study, we tested whether the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels, which are expressed in the heart and activated by protein kinase A and protein kinase C, are important for IPC in isolated heart preparations from wild-type (WT) and CFTR knockout (CFTR-/-) mice. METHODS AND RESULTS: Hearts were isolated from age-matched WT or CFTR-/- (B6.129P2-Cftr(tm1Unc) and STOCKCftr(tm1Unc)-TgN 1Jaw) mice and perfused in the Langendorff or working-heart mode. All hearts were allowed to stabilize for 10 minutes before they were subjected to 30 or 45 minutes of global ischemia followed by 40 minutes of reperfusion (control group) or 3 cycles of 5 minutes of ischemia and reperfusion (IPC group) before 30 or 45 minutes of global ischemia and 40 minutes of reperfusion. Hemodynamic indices were recorded to evaluate cardiac functions. Release of creatine phosphate kinase (CPK) in the samples of coronary effluent and infarct size of the ventricles were used to estimate myocardial tissue injury. In WT adult hearts, IPC protected cardiac function during reperfusion and significantly decreased ischemia-induced CPK release and infarct size. A selective CFTR channel blocker, gemfibrozil, abrogated the protective effect of IPC. Furthermore, targeted inactivation of the CFTR gene in 2 different strains of CFTR-/- mice also prevented IPC's protection of cardiac function and myocardial injury against sustained ischemia. CONCLUSIONS: CFTR Cl- channels may serve as novel and crucial mediators in mouse heart IPC.
Authors:
Hong Chen; Luis L Liu; Linda L Ye; Conor McGuckin; Susan Tamowski; Paul Scowen; Honglin Tian; Keith Murray; William J Hatton; Dayue Duan
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2004-08-02
Journal Detail:
Title:  Circulation     Volume:  110     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-08-10     Completed Date:  2005-02-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  700-4     Citation Subset:  AIM; IM    
Affiliation:
Department of Pharmacology, Center of Biomedical Research Excellence, University of Nevada School of Medicine, Reno, NV 89557-0270, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Chlorides / metabolism
Cystic Fibrosis Transmembrane Conductance Regulator / antagonists & inhibitors,  deficiency*,  genetics,  physiology
Gemfibrozil / pharmacology
Ion Transport / drug effects
Ischemic Preconditioning
Male
Mice
Mice, Inbred C57BL
Mice, Inbred CFTR
Mice, Knockout
Myocardial Ischemia / complications,  genetics,  pathology
Myocardial Reperfusion Injury / genetics,  prevention & control*
Oligopeptides / administration & dosage,  pharmacology
Species Specificity
Ventricular Function, Left
Grant Support
ID/Acronym/Agency:
HL-63914/HL/NHLBI NIH HHS; P-20-RR-15581/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Chlorides; 0/Oligopeptides; 0/Peptamen; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator; 25812-30-0/Gemfibrozil

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


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