Glutathione and K + channel remodeling in postinfarction rat heart

George J Rozanski, Zhi Xu

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Electrical remodeling of the diseased ventricle is characterized by downregulation of K + channels that control action potential repolarization. Recent studies suggest that this shift in electrophysiological phenotype involves oxidative stress and changes in intracellular glutathione (GSH), a key regulator of redox-sensitive cell functions. This study examined the role of GSH in regulating K + currents in ventricular myocytes from rat hearts 8 wk after myocardial infarction (MI). Colorimetric analysis of tissue extracts showed that endogenous GSH levels were significantly less in post-MI hearts compared with controls, which is indicative of oxidative stress. This change in GSH status correlated with significant decreases in activities of glutathione reductase and γ-glutamylcysteine synthetase. Voltage-clamp studies of isolated myocytes from post-MI hearts demonstrated that downregulation of the transient outward K + current (I to ) could be reversed by pretreatment with exogenous GSH or N-acetyl-cysteine, a precursor of GSH. Upregulation of I to was also elicited by dichloroacetate, which increases glycolytic flux through the GSH-related pentose pathway. This metabolic effect was blocked by inhibitors of glutathione reductase and the pentose pathway. These data indicate that oxidative stress-induced alteration in the GSH redox state plays an important role in I to channel remodeling and that GSH homeostasis is influenced by pathways of glucose metabolism.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume282
Issue number6 51-6
StatePublished - Jul 2 2002

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Glutathione
Pentoses
Oxidative Stress
Glutathione Reductase
Myocardial Infarction
Muscle Cells
Oxidation-Reduction
Down-Regulation
Atrial Remodeling
Glutamate-Cysteine Ligase
Tissue Extracts
Action Potentials
Cysteine
Homeostasis
Up-Regulation
Phenotype
Glucose
N-acetylglutathione

Keywords

  • Failure
  • Ion
  • Myocytes
  • Redox

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Glutathione and K + channel remodeling in postinfarction rat heart . / Rozanski, George J; Xu, Zhi.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 282, No. 6 51-6, 02.07.2002.

Research output: Contribution to journalArticle

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