Hypertrophy decreases cardiac K(ATP) channel responsiveness to exogenous and locally generated (glycolytic) ATP

Feng Yuan, Neil R. Brandt, Judith M.B. Pinto, Bernard J. Wasserlauf, Robert J. Myerburg, Arthur L. Bassett

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

This study tests the hypothesis that glycolytic regulation of K(ATP) 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, K(ATP) 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 K(ATP) channels. Single channel conductance in the absence of PEP was similar (70 pS, normal; 66 pS, LVH). However, LVH K(ATP) 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 IC(50,PEP) increased to 23 μM; (11 μM normal). Lactate failed to activate K(ATP) 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 K(ATP) channels (IC(50,ATP) = 283 μM LVH; 93 μM normal). Our data indicate myocardial hypertrophy increases the maximal activity of K(ATP) 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.

Original languageEnglish (US)
Pages (from-to)2837-2848
Number of pages12
JournalJournal of Molecular and Cellular Cardiology
Volume29
Issue number10
DOIs
StatePublished - Oct 1997

Keywords

  • ATP
  • Glycolysis
  • Left ventricular hypertrophy
  • Patch clamp
  • Potassium channels

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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