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Connections: heart disease, cellular electrophysiology, and ion channels
R E ten Eick1, D W Whalley, H H Rasmussen
1Department of Pharmacology, Northwestern University, Chicago, Illinois 60611.
Insights
Myocardial disease and ischemia alter cardiac ion channel function, impacting heart electrical activity. These conditions change cellular environments and directly affect ion channel properties.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Electrophysiology
Background:
- Cardiac electrophysiology relies on ion channels.
- Myocardial disease and ischemia disrupt the heart's cellular environment.
- These disruptions can alter ion channel function.
Purpose of the Study:
- To investigate how myocardial disease and ischemia affect cardiac ion channel electrophysiology.
- To examine changes in intracellular and extracellular environments during ischemia.
- To understand the molecular mechanisms underlying these alterations.
Main Methods:
- Analysis of changes in extracellular and intracellular ion concentrations ([K+], [Na+], [Ca2+]) and pH.
- Assessment of metabolic byproduct accumulation (e.g., lysophosphatidylcholine) and ATP depletion.
- Investigation of alterations in specific potassium (K+) channels, including A-like channels and inward rectifiers.
Main Results:
- Ischemia alters extracellular and intracellular conditions (e.g., pH, ion concentrations, ATP levels).
- Myocardial hypertrophy affects the expression of cardiac A-like channel function.
- Ischemia alters intrinsic conductance properties of the inward rectifier potassium channel.
Conclusions:
- Cardiac ion channel function is significantly altered by myocardial disease and ischemia at the molecular level.
- Changes in cellular milieu and direct effects on channels contribute to altered cardiac electrophysiology.
- Further research into the regulation of cardiac ion channels in disease states is warranted.
Abstract:
Our purpose in this article is to examine the hypothesis that both myocardial disease and ischemia can alter the electrophysiologic function of the ion channels responsible for the cellular electrical activity of the heart. Changes in the intracellular and extracellular milieus occur during ischemia and can alter the electrophysiology of several species of ionic channels and the cellular electrophysiologic activity of cardiac myocytes. Included are 1) changes in extracellular [K+] and pH and in intracellular [Na+], [Ca2+], and pH; 2) accumulation of noxious metabolic products such as lysophosphatidylcholine; and 3) depletion of intracellular ATP. Finally, ischemia or disease (e.g., hypertrophy) can alter the electrophysiology of at least two types of K+ channels, the A-like channels underlying the transient outward current and the inward rectifier, by mechanisms that apparently do not involve alteration of either the intra- or extracellular milieus. Findings suggest that the expression of cardiac A-like channel function can be altered by hypertrophy and that at least one intrinsic conductance property of the inward rectifier can be altered by ischemia. We speculate that the control of expression, function, and regulation of cardiac ion channels can be affected at the molecular level by heart disease and myocardial ischemia.