Inhibition of K+ currents by homocysteine in rat ventricular myocytes

Robert D. Shontz, Zhi Xu, Kaushik P. Patel, George J. Rozanski

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Homocysteine Inhibition of K+ Channels in Rat Cardiomyocytes. Introduction: Clinical evidence suggests that increased blood levels of homocysteine may be an independent risk factor for the development of cardiovascular disease, but the functional effects of this sulfhydryl amino acid on the myocardium are poorly understood. The present study was conducted to determine the direct effects of homocysteine on the electrophysiologic properties of the heart. Methods and Results: Whole-cell voltage-clamp recordings were made in ventricular myocytes isolated from norman rat hearts to analyze the Ca2+-independent, transient outward K+ current (Ito), a major repolarizing current in these cells. Maximum Ito density (measured at +60 mV) was decreased ∼47% from baseline in the presence of 500 μM homocysteine (P < 0.05), but the amount of block varied in a frequency- and voltage-dependent manner. Decreased Ito density was not accompanied by significant changes in voltage- or time-dependent properties of the current, nor was it affected by pretreating myocytes with the protein kinase inhibitor staurosporine. Because a portion of total extracellular homocysteine is oxidized, we examined the response to homocystine, the oxidized form of homocysteine. In myocytes superfused with 500 μM homocystine, maximum Ito density was decreased by ∼40% from baseline (P < 0.05). In contrast, the thiolactone form of homocysteine did not alter Ito amplitude. Conclusion: These data suggest that homocysteine and its oxidized form homocystine acutely inhibit Ito channels in ventricular myocytes by mechanisms involving the free thiol or disulfide moieties of these compounds. High homocysteine or homocystine levels may contribute to abnormal repolarization and arrhythmogenic conditions in the intact heart.

Original languageEnglish (US)
Pages (from-to)175-182
Number of pages8
JournalJournal of Cardiovascular Electrophysiology
Volume12
Issue number2
DOIs
StatePublished - Jan 1 2001

Keywords

  • Cardiomyocytes
  • Electrophysiology
  • Heart
  • Patch clamp
  • Potassium channels

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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