Glutathione and K+ channel remodeling in postinfarction rat heart

George J. Rozanski, Zhi Xu

Research output: Contribution to journalArticle

35 Scopus citations

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 (Ito) could be reversed by pretreatment with exogenous GSH or N-acetyl-cysteine, a precursor of GSH. Upregulation of Ito 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 Ito channel remodeling and that GSH homeostasis is influenced by pathways of glucose metabolism.

Original languageEnglish (US)
Pages (from-to)H2346-H2355
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume282
Issue number6 51-6
StatePublished - Jul 2 2002

Keywords

  • Failure
  • Ion
  • Myocytes
  • Redox

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Glutathione and K<sup>+</sup> channel remodeling in postinfarction rat heart'. Together they form a unique fingerprint.

  • Cite this