Document Detail


Expression of skeletal muscle sodium channel (Nav1.4) or connexin32 prevents reperfusion arrhythmias in murine heart.
MedLine Citation:
PMID:  20823275     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: acute myocardial ischaemia induces a decrease in resting membrane potential [which leads to reduction of action potential (AP) V(max)] and intracellular acidification (which closes gap junctions). Both contribute to conduction slowing. We hypothesized that ventricular expression of the skeletal muscle Na(+) channel, Nav1.4 (which activates fully at low membrane potentials), or connexin32 (Cx32, which is less pH-sensitive than connexin43) would support conduction and be antiarrhythmic. We tested this hypothesis in a murine model of ischaemia and reperfusion arrhythmias.
METHODS AND RESULTS: empty adenovirus (Sham) or adenoviral constructs expressing either SkM1 (gene encoding Nav1.4) or Cx32 genes were injected into the left ventricular wall. Four days later, ventricular tachycardia (VT) occurred during reperfusion following a 5 min coronary occlusion. In Nav1.4- and Cx32-expressing mice, VT incidence and duration were lower than in Sham (P < 0.05). In vitro multisite microelectrode mapping was performed in the superfused right ventricular wall. To simulate ischaemic conditions, [K(+)] in solution was increased to 10 mmol/L and/or pH was decreased to 6.0. Western blots revealed Cx32 and Nav1.4 expression in both ventricles. Nav1.4 APs showed higher V(max) and conduction velocity (CV) than Shams at normal and elevated [K(+)]. Exposure of tissue to acid solution reduced intracellular pH to 6.4. There was no difference in CV between Sham and Cx32 groups in control solution. Acid solution slowed CV in Sham (P < 0.05) but not in Cx32.
CONCLUSION: Nav1.4 or Cx32 expression preserved normal conduction in murine hearts and decreased the incidence of reperfusion VT.
Authors:
Evgeny P Anyukhovsky; Eugene A Sosunov; Yelena N Kryukova; Kevin Prestia; Nazira Ozgen; Mathilde Rivaud; Ira S Cohen; Richard B Robinson; Michael R Rosen
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural     Date:  2010-09-07
Journal Detail:
Title:  Cardiovascular research     Volume:  89     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-17     Completed Date:  2011-04-04     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  41-50     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Arrhythmias, Cardiac / genetics,  physiopathology,  prevention & control*
Connexins / genetics*,  physiology*
Disease Models, Animal
Electrocardiography
Gene Expression
Heart Conduction System / physiopathology
Hydrogen-Ion Concentration
Male
Membrane Potentials
Mice
Mice, Inbred C57BL
Mice, Transgenic
Muscle Proteins / genetics*,  physiology*
Muscle, Skeletal / physiology
Myocardial Reperfusion Injury / genetics,  physiopathology,  prevention & control*
Potassium / metabolism
Rats
Sodium Channels / genetics*,  physiology*
Tachycardia, Ventricular / genetics,  physiopathology,  prevention & control
Grant Support
ID/Acronym/Agency:
HL-094410/HL/NHLBI NIH HHS; R01 HL094410/HL/NHLBI NIH HHS; R01 HL094410-03/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Connexins; 0/Muscle Proteins; 0/Scn4a protein, rat; 0/Sodium Channels; 0/connexin 32; RWP5GA015D/Potassium
Comments/Corrections
Comment In:
Cardiovasc Res. 2011 Jan 1;89(1):4-5   [PMID:  21051418 ]

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


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