Influence of Glucose on the Transmembrane Action Potential of Guinea‐Pig Papillary Muscle: Metabolic Inhibitors, Ouabain, and Calcium Chloride, and their Interaction with Glucose, Sympathomimetic Amines, and Aminophylline

In a previous report, we have proposed that anaerobic glycolysis alone can maintain an action potential of normal duration in guinea-pig papillary muscle. This proposal followed from the observation that 50 mM glucose, several sympathomimetic amines, and aminophylline all caused the duration of the action potential of muscles, which had been reduced by incubation in a medium containing 5 mM glucose, to return toward control values. This occurred in the presence or absence of oxygen. It was further proposed that the ATP resulting from anaerobic glycolysis was in some way preferentially utilized in the membrane by a process controlling repolarization and therefore the duration of the action potential. The present experiments were undertaken to determine what metabolic pathways were necessary for the glucose effect mentioned above, by the use of the metabolic inhibitors sodium cyanide, iodoacetic acid, and 2,4-dinitrophenol. Secondly, the effects of ouabain and calcium, which are known to modulate the utilization of ATP, on the glucose effect were studied. It was concluded that an intact glycolytic pathway is necessary for the effect of glucose on the electrical activity of papillary muscle and that the effect can be increased or decreased by low or high doses of ouabain, respectively. The actions of ouabain are thought to be due to a stimulation and depression of a membrane ATP-ase.

[1]  R. Havel,et al.  Effects of Ouabain on Force of Contraction, Oxygen Consumption, and Metabolism of Free Fatty Acids in the Perfused Rabbit Heart , 1967, Circulation research.

[2]  B. Jeanrenaud,et al.  Insulin-like action of ouabain. I. Effect on carbohydrate metabolism. , 1967, Biochimica et biophysica acta.

[3]  H. Matsui,et al.  Purification and properties of a highly active ouabain-sensitive Na+, K+-dependent adenosinetriphosphatase from cardiac tissue. , 1966, Biochimica et biophysica acta.

[4]  P. Müller Ouabain Effects on Cardiac Contraction, Action Potential, and Cellular Potassium , 1965, Circulation research.

[5]  J C SKOU,et al.  ENZYMATIC BASIS FOR ACTIVE TRANSPORT OF NA+ AND K+ ACROSS CELL MEMBRANE. , 1965, Physiological reviews.

[6]  E. Daniel,et al.  Influence of Glucose on the Transmembrane Action Potential of Anoxic Papillary Muscle , 1965, The Journal of general physiology.

[7]  H C LUETTGAU,et al.  The effect of metabolic inhibitors on the fatigue of the action potential in single muscle fibres , 1965, The Journal of physiology.

[8]  B. R. Nechay,et al.  BIPHASIC RENAL EFFECTS OF OUABAIN IN THE CHICKEN: CORRELATION WITH A MICROSOMAL NA+-K+ STIMULATED ATP-ASE. , 1964, The Journal of pharmacology and experimental therapeutics.

[9]  K. S. Lee,et al.  A STUDY OF THE SODIUM- AND POTASSIUM-ACTIVATED ADENOSINETRIPHOSPHATASE ACTIVITY OF HEART MICROSOMAL FRACTION. , 1963, Biochemical pharmacology.

[10]  W. C. Yang,et al.  ANAEROBIC FUNCTIONAL ACTIVITY OF ISOLATED RABBIT ATRIA. , 1963, The American journal of physiology.

[11]  D. G. Kassebaum Electrophysiological effects of strophanthin in the heart. , 1963, The Journal of pharmacology and experimental therapeutics.

[12]  W. V. Macfarlane The Plateau of the Action Potential of the Frog Ventricle , 1960, Circulation research.

[13]  J. R. Simons The blood pressure and the pressure pulses in the arterial arches of the frog (Rana temporaria) and the toad (Bufo bufo) , 1957, The Journal of physiology.

[14]  Caldwell Pc The effects of certain metabolic inhibitors on the phosphate esters of the squid giant axon. , 1956 .

[15]  A. J. Brady,et al.  Intracellular recording from moving tissues with a flexibly mounted ultramicroelectrode. , 1956, Science.

[16]  C. E. Kossmann,et al.  The action of iodoacetate on the electrical and mechanical activities of the isolated perfused frog heart. , 1955, The Journal of clinical investigation.

[17]  J. Marshall Action of iodoacetic acid, 2,4 dinitrophenol, and L-triiodothyronine on the electrical response of the myocardium. , 1955, The American journal of physiology.

[18]  M. Wilson,et al.  The action of iodoacetate on the isolated rabbit auricle. , 1954, The Journal of pharmacology and experimental therapeutics.

[19]  J. L. Webb The actions of metabolic substrates and inhibitors on the rabbit auricle. , 1950, British journal of pharmacology and chemotherapy.

[20]  P. Saunders,et al.  The metabolism of the heart in relation to drug action; the action of metabolic inhibitors on rat heart slice respiration. , 1949, Archives of biochemistry.

[21]  W. Loomis,et al.  Reversible inhibition of the coupling between phosphorylation and oxidation. , 1948, The Journal of biological chemistry.

[22]  J. Tepperman,et al.  A spectrophotometric study of the competition of methemoglobin and cytochrome oxidase for cyanide in vitro. , 1946, The Journal of biological chemistry.

[23]  D. E. Green,et al.  Dismutations and oxidoreductions. , 1937, The Biochemical journal.

[24]  M. Dixon Action of lodoacetate on Dehydrogenases and Alcoholic Fermentation , 1937, Nature.

[25]  P. Müller EFFECT OF OUABAIN ON CARDIAC CONTRACTION, ACTION POTENTIAL AND CELLULAR POTASSIUM* , 1964 .

[26]  J C SKOU,et al.  The influence of some cations on an adenosine triphosphatase from peripheral nerves. , 1957, Biochimica et biophysica acta.