Metabolism and the electrical activity of anoxic ventricular muscle

Abstract

SUMMARY1. The action potential duration of anoxic guinea-pig ventricular muscle was related to ATP generated by glycolysis. In 50 mm glucose medium the action potential duration was maintained; in 5 mm glucose medium the action potential duration shortened, the glycolytic rate declined and the ATP content was reduced.2. The action potential amplitude was related to the metabolic state of the muscle but not to the intracellular sodium concentration.3. It is suggested that changes in the action potential duration and overshoot in anoxic muscle may be due to an influence of metabolism on the slow inward current.4. Anoxic muscle incubated for 8 hr in 5 mm glucose medium had an Em of -77*1 mV compared to -81-1 mV in fresh muscle. The calculated Ek of anoxic muscle was -47*4 mV.5. The resting potential of anoxic muscle was separated into two components, one dependent on potassium distribution and the other on the activity of an electrogenic sodium pump.6. The electrogenic pump component was stimulated upon raising the glucose concentration of the medium or upon raising the external potassium concentration.7. The electrogenic pump component was inhibited by ouabain or by reduction of the temperature from 35 to 80 C.

Functional interaction between K(ATP) channels and the Na(+)‐K(+) pump in metabolically inhibited heart cells of the guinea‐pig.

“…This is 2-5 times faster than the time needed to wash the drug out completely [ATP] in the submembrane pool than is present in the rest of the cytoplasm (Jones, 1986). The idea of functionally compartmentalized ATP is in line with the results of numerous groups, who have shown that it is preferentially glycolytic ATP which influences membrane proteins (McDonald & MacLeod, 1973;Bricknell, Daries & Opie, 1981;Hasin & Barry, 1984), including cardiac KATP channels (Weiss & Lamp, 1987. In our experiments…”

Glucose for the Heart

“…Although the exact mechanisms for the effects of glucose and insulin in the ischemic myocardium are not known, it seems reasonable to assume that they enhance membrane stability. 104,138 Shortly after, it was also observed that GIK decreases the infarct size after coronary artery ligation in dogs, lessens ultrastructural damage, and improves global contractile function of the heart. 139 The infusion of GIK was shown to reduce the frequency and duration of ventricular arrhythmias and to improve the survival of patients after myocardial infarction.…”

“…45 Glycolysis during ischemia seems particularly important in providing a residual production of ATP. Such production sustains the activity of ATPrequiring enzymes, mainly the sarcolemmal Na ϩ ,K ϩ -ATPase 103,104 and the sarcoendoplasmic Ca 2ϩ -ATPase.…”

Metabolic changes during ischaemia and their role in contractile failure in isolated ferret hearts.

“…It is well known that there is a decline in both the amplitude and the duration of the cardiac action potential during ischaemia (Downar, Janse & Durrer, 1977;Russell, Smith & Oliver, 1979), and such changes could clearly reduce both Ca2+ influx across the plasmalemma and Ca2+ release from the sarcoplasmic reticulum. A similar mechanism is now well established under conditions of metabolic blockade (inhibition of both aerobic and anaerobic metabolism), when dramatic action potential shortening occurs (McDonald & MacLeod, 1973; Allen, Harris & Smith, 1987; Lederer, Nichols & Smith, 1989;Elliott, Smith & Allen, 1989), leading to a failure of Ca2+ release (Allen & Orchard, 1983) and therefore to mechanical failure (Stern, Silverman, Houser, Josephson, Capogrossi, Nichols, Lederer & Lakatta, 1988;Lederer et al 1989). …”