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Myocardial metabolic inhibition and membrane potential, contraction, and potassium uptake
Abstract:
Interruption of synthesis of ATP during hypoxia or ischemia can produce membrane depolarization that may be related to inhibition of Na+-K+-ATPase. To examine this hypothesis, the effects of exposure of cultured chick embryo ventricular cells to 1 mM cyanide (CN), to 20 mM 2-deoxy-D-glucose (2-DG), to CN + 2-DG, and to ouabain (10(-3) M) on contraction, membrane potential, and 42K uptake were determined. CN produced moderate membrane depolarization and electromechanical uncoupling within 2 min. 2-DG caused marked membrane depolarization with a transient negative inotropic effect. Exposure to CN + 2-DG produced marked depolarization (-38 mV) and mechanical arrest of the cells in a relaxed state. Ouabain produced marked depolarization (-39 mV) and contracture of the cells. Uptake of 42K was inhibited by 10(-3) M ouabain within seconds. However, CN + 2-DG produced no inhibition of 42K uptake within the first 2 min of exposure, and inhibition of the Na pump by CN + 2-DG required 30 min to develop fully. Exposure to CN alone produced no inhibition of 42K uptake, whereas moderate inhibition was produced by 2-DG alone even when substrate for oxidative phosphorylation was provided. We conclude that the acute effects of inhibition of glycolysis and oxidative phosphorylation on membrane potential and contraction in these cells are not due to inhibition of the Na pump and that during partial metabolic inhibition active univalent cation transport in these cells is relatively dependent on ATP derived from glycolysis, whereas contraction is more dependent on ATP supplied by oxidative phosphorylation.
Insights
Hypoxia and ischemia disrupt ATP synthesis, affecting cell membranes. This study shows acute effects on cell contraction and membrane potential are not due to Na+-K+-ATPase inhibition.
Area of Science:
- Cardiology
- Cell Physiology
- Biochemistry
Background:
- Interruption of ATP synthesis during hypoxia or ischemia can lead to membrane depolarization.
- This depolarization is potentially linked to the inhibition of the sodium-potassium adenosine triphosphatase (Na+-K+-ATPase).
Purpose of the Study:
- To investigate the effects of inhibiting ATP synthesis on cardiac cell function.
- To determine if Na+-K+-ATPase inhibition mediates the observed membrane depolarization and functional changes.
Main Methods:
- Cultured chick embryo ventricular cells were exposed to cyanide (CN), 2-deoxy-D-glucose (2-DG), CN + 2-DG, or ouabain.
- Measurements included cell contraction, membrane potential, and 42K uptake.
Main Results:
- Cyanide and 2-DG caused membrane depolarization and altered contractility.
- Combined CN + 2-DG induced significant depolarization and mechanical arrest.
- Ouabain caused depolarization and contracture, with rapid inhibition of 42K uptake.
- CN + 2-DG did not acutely inhibit 42K uptake, indicating delayed Na+-K+-ATPase inhibition.
Conclusions:
- Acute effects of metabolic inhibition on cardiac cell membrane potential and contraction are not mediated by immediate Na+-K+-ATPase inhibition.
- Cellular ATP production from glycolysis supports univalent cation transport, while oxidative phosphorylation is more critical for contraction during partial metabolic inhibition.