Altered K+ current of ventricular myocytes in rats with chronic myocardial infarction

George J. Rozanski, Zhi Xu, Kun Zhang, Kaushik P. Patel

Research output: Contribution to journalArticle

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Abstract

The aim of the present study was to define the cellular mechanisms underlying changes in K+ channel function in the failing heart after myocardial infarction. Rats with left coronary artery ligation were prepared and allowed to recover for 16 wk before study. Animals with chronic infarction exhibited marked cardiac hypertrophy and signs of heart failure, as indicated by a nearly twofold increase in heart weight- and lung weight- to-body weight ratios, respectively, compared with time-matched controls. Cardiac hypertrophy was also evident by a 49% increase in whole cell capacitance of isolated left ventricular myocytes (P < 0.05). Voltage-clamp experiments revealed that the maximum density of the Ca2+-independent, transient outward current (It(o)), measured at +60 mV, was 42% less in myocytes from infarcted hearts than in myocytes from control hearts (P < 0.05), whereas the inward rectifier current (I(K1)) density was not different between groups. The reduced I(to) density in the infarcted group was reversed, however, in 4-5 h by treatment with exogenous dichloroacetate or pyruvate, both activators of pyruvate dehydrogenase. Moreover, control myocytes incubated for 6 h in the presence of an inhibitor of pyruvate dehydrogenae, 3-bromopyruvate, exhibited a concentration-dependent decrease in I(to) density compared with untreated cells. the present data demonstrate that I(to) density is reversibly decreased surviving myocytes from infarcted hearts and suggest that mechanisms related to glucose metabolism via pyruvate dehydrogenase may be involved. These postinfarction changes in myocyte I(to) channel function may relate to impared contractility and arrhythmogenesis, which are characteristic of the intact, failing heart.

Original languageEnglish (US)
Pages (from-to)H259-H265
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume274
Issue number1 43-1
StatePublished - Jan 1 1998

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Muscle Cells
Myocardial Infarction
Pyruvic Acid
Cardiomegaly
Weights and Measures
Infarction
Ligation
Coronary Vessels
Oxidoreductases
Heart Failure
Body Weight
Glucose
Lung

Keywords

  • Potassium channels
  • Pyruvate dehydrogenase

ASJC Scopus subject areas

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

Cite this

Altered K+ current of ventricular myocytes in rats with chronic myocardial infarction. / Rozanski, George J.; Xu, Zhi; Zhang, Kun; Patel, Kaushik P.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 274, No. 1 43-1, 01.01.1998, p. H259-H265.

Research output: Contribution to journalArticle

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