Document Detail

Glycolytic inhibition causes spontaneous ventricular fibrillation in aged hearts.
MedLine Citation:
PMID:  21478408     Owner:  NLM     Status:  MEDLINE    
Selective glycolytic inhibition (GI) promotes electromechanical alternans and triggered beats in isolated cardiac myocytes. We sought to determine whether GI promotes triggered activity by early afterdepolarization (EAD) or delayed afterdepolarizations in intact hearts isolated from adult and aged rats. Dual voltage and intracellular calcium ion (Ca(i)(2+)) fluorescent optical maps and single cell glass microelectrode recordings were made from the left ventricular (LV) epicardium of isolated Langendorff-perfused adult (∼4 mo) and aged (∼24 mo) rat hearts. GI was induced by replacing glucose with 10 mM pyruvate in oxygenated Tyrode's. Within 20 min, GI slowed Ca(i)(2+) transient decline rate and shortened action potential duration in both groups. These changes were associated with ventricular fibrillation (VF) in the aged hearts (64 out of 66) but not in adult hearts (0 out of 18; P < 0.001). VF was preceded by a transient period of focal ventricular tachycardia caused by EAD-mediated triggered activity leading to VF within seconds. The VF was suppressed by the ATP-sensitive K (K(ATP)) channel blocker glibenclamide (1 μM) but not (0 out of 7) by mitochondrial K(ATP) block. The Ca-calmodulin-dependent protein kinase II (CaMKII) blocker KN-93 (1 μM) prevented GI-mediated VF (P < 0.05). Block of Na-Ca exchanger (NCX) by SEA0400 (2 μM) prevented GI-mediated VF (3 out of 6), provided significant bradycardia did not occur. Aged hearts had significantly greater LV fibrosis and reduced connexin 43 than adult hearts (P < 0.05). We conclude that in aged fibrotic unlike in adult rat hearts, GI promotes EADs, triggered activity, and VF by activation of K(ATP) channels CaMKII and NCX.
Norishige Morita; Jong-Hwan Lee; Aneesh Bapat; Michael C Fishbein; William J Mandel; Peng-Sheng Chen; James N Weiss; Hrayr S Karagueuzian
Related Documents :
9632378 - The alzheimer's plaques, tangles and memory deficits may have a common origin. part iii...
22547068 - Nad+ levels control ca2+ store replenishment and mitogen-induced increase of cytosolic ...
22695678 - Na(+),k (+)-atpase as a docking station: protein-protein complexes of the na(+),k (+)-a...
22285408 - Relaxation of rat thoracic aorta by fibrate drugs correlates with their potency to dist...
18467868 - Effects of calcium ion concentration on starch hydrolysis of barley alpha-amylase isozy...
18945888 - Modulation of sk channel trafficking by beta adrenoceptors enhances excitatory synaptic...
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural     Date:  2011-04-08
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  301     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-06-30     Completed Date:  2011-08-30     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H180-91     Citation Subset:  IM    
Translational Arrhythmia Research Section, Cardiovascular Research Laboratory, David Geffen School of Medicine at UCLA, 675 Charles E. Young Dr. South, MRL 3645 Mail Code: 176022, Los Angeles, CA 90095, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Action Potentials / physiology
Adenosine Triphosphate / metabolism
Aging / physiology*
Arrhythmia, Sinus / physiopathology
Calcium / metabolism,  physiology
Calcium Signaling / physiology
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / drug effects,  metabolism
Connexin 43 / metabolism
Electrophysiological Phenomena / physiology
Endocardium / physiology
Fibrosis / pathology
Fluorescent Dyes
Glycolysis / drug effects*
Heart / physiopathology*
KATP Channels / drug effects,  metabolism
Rats, Inbred F344
Sodium-Calcium Exchanger / drug effects,  metabolism
Tachycardia, Ventricular / physiopathology
Ventricular Fibrillation / chemically induced*,  physiopathology
Grant Support
Reg. No./Substance:
0/Connexin 43; 0/Fluorescent Dyes; 0/KATP Channels; 0/Sodium-Calcium Exchanger; 56-65-5/Adenosine Triphosphate; 7440-70-2/Calcium; EC Protein Kinase Type 2

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

Previous Document:  H2O2 preconditioning modulates phase II enzymes through p38 MAPK and PI3K/Akt activation.
Next Document:  Sex differences in physiological cardiac hypertrophy are associated with exercise-mediated changes i...