Related Experiment Video
Updated: Jul 30, 2026
Acute Myocardial Infarction in Rats
Published on: February 16, 2011
Altered K+ current of ventricular myocytes in rats with chronic myocardial infarction
1Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198-4575, USA.
Insights
Following heart attack, K+ channel function (Ito) decreases in surviving heart cells. This reduction is reversible and linked to impaired glucose metabolism via pyruvate dehydrogenase, impacting heart contractility.
Area of Science:
- Cardiology
- Cellular Physiology
- Molecular Biology
Background:
- Myocardial infarction (MI) leads to heart failure, characterized by altered cardiac function.
- Cellular mechanisms of K+ channel dysfunction in failing hearts post-MI remain incompletely understood.
Purpose of the Study:
- To investigate the cellular mechanisms behind altered K+ channel function in the failing heart after myocardial infarction.
- To identify specific K+ currents affected and their relationship to metabolic pathways.
Main Methods:
- Rats underwent left coronary artery ligation and recovered for 16 weeks to induce chronic myocardial infarction and heart failure.
- Cardiac hypertrophy was assessed via heart/lung weight-to-body weight ratios and myocyte cell capacitance.
- Voltage-clamp techniques were used to measure ion channel current densities (transient outward K+ current [Ito] and inward rectifier K+ current [IK1]) in isolated ventricular myocytes.
Main Results:
- Animals with chronic MI showed significant cardiac hypertrophy and heart failure indicators.
- Myocytes from infarcted hearts exhibited a 42% reduction in Ito density compared to controls; IK1 density remained unchanged.
- Treatment with dichloroacetate or pyruvate (pyruvate dehydrogenase activators) reversed the reduced Ito density in infarcted myocytes.
- Inhibition of pyruvate dehydrogenase in control myocytes decreased Ito density, suggesting a metabolic link.
Conclusions:
- Transient outward K+ current (Ito) density is reversibly decreased in surviving myocytes of infarcted hearts.
- Mechanisms involving glucose metabolism via pyruvate dehydrogenase are implicated in these post-infarction changes.
- Altered myocyte Ito function may contribute to impaired contractility and arrhythmogenesis in the failing heart.
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 Ca(2+)-independent, transient outward current (I.t.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 (IK1) density was not different between groups. The reduced Ito 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 dehydrogenase, 3-bromopyruvate, exhibited a concentration-dependent decrease in Ito density compared with untreated cells. The present data demonstrate that Ito density is reversibly decreased in surviving myocytes from infarcted hearts and suggest that mechanisms related to glucose metabolism via pyruvate dehydrogenase may be involved. These postinfarction changes in myocyte Ito channel function may relate to impaired contractility and arrhythmogenesis, which are characteristic of the intact, failing heart.
