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D P MacLeod

Publications and source records attributed to D P MacLeod.

17 recordsLinked to original sources
PubMed1973

Metabolism and the electrical activity of anoxic ventricular muscle.

1. 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 E(m) of -77.1 mV compared to -81.1 mV in fresh muscle. The calculated E(k) 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 8 degrees C.

Action Potentials↗
PubMed1973

DNP-induced dissipation of ATP in anoxic ventricular muscle.

1. During aerobic incubation in 5 mM glucose medium, 10(-5) M-DNP reduced the action potential duration and amplitude and the developed tension of guinea-pig ventricular muscle more rapidly and to a greater extent than anoxia.2. The DNP effect on electrical and mechanical activity was even more pronounced following prolonged anoxic incubation. Since the action potential duration and developed tension of anoxic ventricular muscle have previously been shown to be dependent on glycolytic ATP, and since the effects of DNP could not be duplicated with NaCN, it was concluded that DNP was exerting an effect in addition to its uncoupling of oxidative phosphorylation.3. Anoxic muscle was incubated with 10(-4) M-IAA or with 10(-4) M-IAA + 10(-4) M-DNP. The ATP content of IAA-treated muscle was significantly lower than control but in the presence of both IAA and DNP there was a further reduction in ATP and an increased lactate production.4. Sodium azide (10(-2) M), a potent inhibitor of mitochondrial ATPase, did not prevent the reduction of ATP in DNP-treated anoxic muscle.5. Ouabain (10(-7) M) partially prevented the rapid decline of action potential duration and developed tension of DNP-treated anoxic muscle. In addition, the glycoside partially blocked the DNP-induced break-down of ATP and stimulation of lactate production.6. Oligomycin (10 mug/ml.) partially prevented the reduction in action potential duration and developed tension of DNP-treated anoxic muscle.7. It was concluded that DNP induces an ;energy leak' by actively promoting the hydrolysis of an high energy glycolytic intermediate at least one step beyond the sites of ATPase inhibition by ouabain and oligomycin.

Action Potentials↗
PubMed1972

The effect of 2,4-dinitrophenol on electrical and mechanical activity, metabolism and ion movements in guinea-pig ventricular muscle.

1. DNP (2,4-dinitrophenol) reduced the duration of the action potential of guinea-pig ventricular muscle at a greater rate than did anoxia. The effect was dose-dependent and was modified by the concentration of glucose in the medium. DNP (0.1 mM) reduced the amplitude of the action potential of muscles incubated with 5 mM glucose; on raising the glucose concentration to 50 mM the effect was reversed.2. A large dose-dependent loss of K(+) occurred within 15 min of incubation with DNP and was attributed to increased efflux. K(+) loss was not related to Na(+) gain during the first 60 min of incubation; during the first 30 min DNP-treated muscle did not gain any Na(+). Although the shortening of the action potential by DNP during aerobic incubation was similar to that of muscles incubated under anaerobic conditions in glucose-free medium, the anaerobic incubation was not associated with increased (42)K efflux.3. It was concluded that the reduction in duration of the action potential was not necessarily the result of an increased K(+) efflux. The effect of DNP on (42)K efflux is considered to result from a direct effect on the cell membrane; the effect on electrical activity may be a combination of the increase in K(+) efflux and a reduction in the inward current due to Na(+) and Ca(++) previously assumed to be dependent on the glycolytic production of ATP.4. Electrogenic Na(+) pumping may contribute to the maintenance of resting potential in K(+)-depleted, DNP-treated cardiac muscle.

Action Potentials↗
PubMed1969

Influence of glucose on the transmembrane action potential of papillary muscle. Effects of concentration, phlorizin and insulin, nonmetabolizable sugars, and stimulators of glycolysis.

The action potential duration (APD) of isolated guinea pig papillary muscle is directly related to the medium glucose concentration regardless of the gas mixture with which it is in equilibrium. The APD can be maintained at control value for many hours by a glucose concentration of 50 mM in the complete absence of oxygen. Following reduction of the APD by incubation of the muscle in medium containing 5 mM glucose, adjustment of the glucose concentration to 50 mM will cause restoration of normal APD. Phlorizin has been shown to competitively interfere with the effect of glucose on the APD and insulin to prevent or reverse the effect of phlorizin. Nonmetabolizable sugars cannot produce glucose-like effects on the APD. Adrenaline, noradrenaline, and isopropylnoradrenaline increased the reduced APD of papillary muscles incubated in the absence of oxygen in a medium containing 5 mM glucose coincident with an increase in contractile force. The effect of isopropylnoradrenaline was blocked by acetylcholine and propranolol. In the presence of iodoacetate and 2-deoxyglucose, isopropylnoradrenaline increased contractile force but not the reduced APD. Aminophylline was found to produce changes in the reduced APD similar to those caused by the sympathomimetic amines. The findings clearly support the hypothesis that anaerobic metabolism utilizing either glycogen or exogenous glucose is capable of maintaining normal transmembrane electrical activity in guinea pig papillary muscle.

Action Potentials↗