Metabolic basis of decreased transient outward K+ current in ventricular myocytes from diabetic rats

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

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45 Scopus citations

Abstract

The purpose of this study was to examine the mechanisms of alterations in cardiac K+ channel function in early stages of experimental diabetes mellitus induced by streptozotocin. Transient outward (I(to)) and inward rectifier (I(K1)) K+ currents were recorded by the whole cell voltage-clamp technique in ventricular myocytes isolated from hearts of 2- to 4-wk diabetic and age-matched control rats. I(to) density in myocytes from diabetic cats was ~30%. Less than control (at + 60 mV; P < 0.01) under basal recording conditions in the presence of 18 mM external glucose, whereas I(K1) density was not different between groups. When external glucose concentration was decreased to 5 mM for 4-6 h, basal I(to) density was not changed in either group of myocytes. To further examine the possible metabolic basis of reduced I(to) density in myocytes from diabetic rats, we separately tested three structurally different compounds that affect substrate utilization in cardiac myocytes: insulin (0.1 μM), dichloroacetate (1.5 mM), and L-carnitine (10 mM). Each compound completely normalized I(to) density in myocytes from diabetic rats treated in vitro for 4-6 h. The same agents had no effect on I(to) density in control myocytes, nor was I(K1) altered in either group of cells. These data provide the first evidence to support the hypothesis that there is a metabolic basis for decreased I(to) density in diabetic rat ventricular myocytes in early stages of this model. Furthermore, our data suggest that depressed glucose metabolism in the diabetic heart may be a key factor underlying changes in I(to) channel function, because agents that increase glucose utilization normalize I(to) density within a short time period.

Original languageEnglish (US)
Pages (from-to)H2190-H2196
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume271
Issue number5 40-5
DOIs
StatePublished - Nov 1996

Keywords

  • L-carnitine
  • dichloroacetate
  • heart
  • insulin

ASJC Scopus subject areas

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

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