Molecular correlates of altered expression of potassium currents in failing rabbit myocardium

Jochen Rose, Antonis A. Armoundas, Yanli Tian, Deborah DiSilvestre, Miroslava Burysek, Victoria Halperin, Brian O'Rourke, David A. Kass, Eduardo Marbán, Gordon F. Tomaselli

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Abstract

Action potential (AP) prolongation is a hallmark of failing myocardium. Functional downregulation of K currents is a prominent feature of cells isolated from failing ventricles. The detailed changes in K current expression differ depending on the species, the region of the heart, and the mechanism of induction of heart failure. We used complementary approaches to study K current downregulation in pacing tachycardia-induced heart failure in the rabbit. The AP duration (APD) at 90% repolarization was significantly longer in cells isolated from failing hearts compared with controls (539 ± 162 failing vs. 394 ± 114 control, P < 0.05). The major K currents in the rabbit heart, inward rectifier potassium current (IK1) transient outward (I to), and delayed rectifier current (IK) were functionally downregulated in cells isolated from failing ventricles. The mRNA levels of Kv4.2, Kv1.4, KChIP2, and Kir2.1 were significantly downregulated, whereas the Kv4.3, Erg, KvLQT1, and minK were unaltered in the failing ventricles compared with the control left ventricles. Significant downregulation in the long splice variant of Kv4.3, but not in the total Kv4.3, Kv4.2, and KChIP2 immunoreactive protein, was observed in cells isolated from the failing ventricle with no change in Kv1.4, KvLQT1, and in Kir2.1 immunoreactive protein levels. Multiple cellular and molecular mechanisms underlie the downregulation of K currents in the failing rabbit ventricle.

Original languageEnglish (US)
Pages (from-to)H2077-H2087
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume288
Issue number5 57-5
DOIs
Publication statusPublished - May 1 2005
Externally publishedYes

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Keywords

  • Action potential
  • Heart failure
  • I
  • I
  • I

ASJC Scopus subject areas

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

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