Document Detail


Hypertrophy decreases cardiac KATP channel responsiveness to exogenous and locally generated (glycolytic) ATP.
MedLine Citation:
PMID:  9344777     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study tests the hypothesis that glycolytic regulation of KATP channel activity is altered in myocardial hypertrophy. Left ventricular (LV) subendocardial myocytes were isolated from cats with normal or left ventricular hypertrophied hearts (LVH). Saponin-permeabilized open cell-attached patch configurations of normal and LVH cells were exposed to an exogenous ATP consuming system containing hexokinase and 2-deoxyglucose. Phosphoenol pyruvate (PEP, substrate for the last ATP producing step in glycolysis) was applied extracellularly; ADP was present. In both cell types, KATP channels were activated in the absence of PEP, inhibited when PEP was added and activated again when PEP was removed, indicating the cells retained metabolic integrity and generated ATP in the proximity of their KATP channels. Single channel conductance in the absence of PEP was similar (70 pS, normal; 66 pS, LVH). However, LVH KATP channels showed enhanced activity (P0=0.50+/-0.03); normal (0.41+/-0.03) in PEP absence (P<0. 05). PEP responsiveness was reduced in LVH, with IC50, PEP increased to 23 microM; (11 microM normal). Lactate failed to activate KATP channels in both cell types. The concentration-P0 response curves obtained during exposure of open cells to exogenous ATP also revealed reduced responsiveness to ATP of LVH KATP channels (IC50, ATP=283 microM LVH; 93 microM normal). Our data indicate myocardial hypertrophy increases the maximal activity of KATP channels in the absence of ATP and reduces their responsiveness to ATP, including locally generated glycolytic ATP. These alterations in metabolic regulation of myocardial electrophysiology may contribute to diversity of action potential shortening in hypertrophied hearts during acute ischemia.
Authors:
F Yuan; N R Brandt; J M Pinto; B J Wasserlauf; R J Myerburg; A L Bassett
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  29     ISSN:  0022-2828     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  1997 Oct 
Date Detail:
Created Date:  1998-02-03     Completed Date:  1998-02-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  2837-48     Citation Subset:  IM    
Copyright Information:
Copyright 1997 Academic Press Limited.
Affiliation:
Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL 33136, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism*,  pharmacology
Animals
Cats
Cell Membrane Permeability
Female
Glycolysis
Hypertrophy, Left Ventricular / metabolism*
Lactic Acid / pharmacology
Male
Myocardium / metabolism*
Phosphoenolpyruvate / pharmacology
Potassium Channels / drug effects,  metabolism*
Grant Support
ID/Acronym/Agency:
HL 19044/HL/NHLBI NIH HHS; HL 21735/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Potassium Channels; 50-21-5/Lactic Acid; 56-65-5/Adenosine Triphosphate; 73-89-2/Phosphoenolpyruvate

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