The Action of Iodoacetate on the Electrical and Mechanical Activities of the Isolated Perfused Frog Heart 1

Kleinfeld, Morris; Stein, Edward; Magin, John; Kossmann, Charles E.

doi:10.1172/jci103235

Cited by 13 publications

(6 citation statements)

References 12 publications

(16 reference statements)

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“…These findings are in agreement with those in the frog ventricle (13,14), in rabbit auricle (15,16), in turtle ventricular strips (17), in rat auricle and dog and cat ventricular muscle (18). The iodoacetate-induced reduction in duration of the action potential in the presence of 5% CO 2 in O 2 was slow, indicating that certain aerobic pathways for oxidation of metabolites such as lactate and pyruvate are unaffected by iodoacetate.…”

Section: Discussionsupporting

confidence: 86%

Influence of Glucose on the Transmembrane Action Potential of Guinea-Pig Papillary Muscle

Prasad

MacLeod

1969

Circulation Research

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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 m\i 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. ADDITIONAL KEY WORDS duration of action potential glycolysis ATP anoxia contractile force repolarizationFrom the

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Section: Discussionsupporting

confidence: 86%

Influence of Glucose on the Transmembrane Action Potential of Guinea-Pig Papillary Muscle

Prasad

MacLeod

1969

Circulation Research

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“…Metabolic inhibitors such as DNP and iodoacetate are known to accelerate repolarization of action potentials of S-A nodes, atrio-ventricular nodes, atria (DeMello, 1959) and ventricles (Kleinfeld, Stein, Magin & Kossmann, 1955;Marshall, 1955) before the resting potential is appreciably affected. The electrophysiological effect of the metabolic inhibitors is partially reversed by ATP (Kleinfeld et al 1955;DeMello, 1959). The repolarization velocity is similarly accelerated by a SHinhibitor, N-ethylmaleimide, but is not affected when the inhibitor is mixed previously with an isomolar concentration of cysteine (unpublished data).…”

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confidence: 99%

Influence of sodium ions on the membrane potential of the sino‐atrial node in response to sympathetic nerve stimulation

Toda¹

1968

The Journal of Physiology

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SUMMARY1. Sympathetic nerve-atrial preparations isolated from rabbits were used in the present study. Transmembrane potentials were recorded from sino-atrial (S-A) nodal pace-maker fibres.2. A reduction of [Na+]o (extracellular concentration of sodium ions) decreased the maximal diastolic potential, reduced the size of the overshoot, prolonged the depolarization time, increased the rate of early repolarization and decreased the rate of late repolarization.3. A Na+-deficiency markedly augmented the positive chronotropic effect of stimulation of post-ganglionic sympathetic nerves at a frequency of 5/sec but slightly augmented the effect of stimulation at 1 and 20/sec. 4. The marked membrane effect of sympathetic nerve stimulation at low [Na+]o was an increase in the slope of slow depolarization during diastole.Corresponding to an induced acceleration of S-A nodal rate, the 90 % duration of the action potential was decreased but the other action potential parameters measured were not influenced.5. A reduction of [Na+]o to 51 7 mm produced in the pace-maker membrane, subthreshold oscillations the rate and the amplitude of which were increased by sympathetic nerve stimulation until conducted potentials were generated.6. It is presumed that cardiac noradrenaline elicits an increase in the slope of slow depolarization during late diastole which is due to an increase in Na+ permeability, a decrease in K+ permeability or a nonselective increase in ion permeability, but that it does not influence the pace-maker membrane during systole.

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“…Azide has been shown to reduce the duration of the action potential plateau in frog heart. 7 The action of iodoacetate on the frog heart seems to be similar to that on rat atrium, 8 the most consistent change being a shortening of the action potential with decrease in stroke volume, the resting potential remaining relatively unaffected. It is probable that one major control of cardiac contractility is the course of depolarization and repolarization preceding contraction and hence the rates at which ion transfer across the membrane occurs.…”

Section: Discussionmentioning

confidence: 89%

Effects of Enzyme Inhibitors on the Contractility and Membrane Potentials of the Rat Atrium

Webb

Hollander

1959

Circulation Research

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Enzyme inhibitors alter the rate of ion movement across the membrane of the rat atrial cell during the repolarization phase. There is simultaneously no constant change in the resting potential while the action potential amplitude is usually depressed to a moderate degree. The relationship between these membrane changes and the altered contractility is investigated. It is concluded that metabolic depression reduces the contractility by two mechanisms: one is a membrane effect, the result of the shortening of the action potential duration, and the other is an effect more directly on the contractile processes. D ISTURBANCE of metabolism in rat atrium alters the contractile and membrane electric properties in a characteristic manner. 1The present study was undertaken to extend the types of metabolic depression, using a variety of enzyme inhibitors which exert their actions on different metabolic systems. A comparison of the different effects of these inhibitors may provide some insight into the relationships between specific metabolic pathways and the functional activity of the atrium. The effects that are common to all types of metabolic depression may indicate how the phenomena of ion transfer and contraction depend on the energy-supplying oxidative processes. METHODSThe membrane potentials and mechanical activity of rat atria (electrically stimulated at a rate of 200/min. in Krebs-Ringer-bicarbonate medium at pH 7.4 and 30 C.) were determined simultaneously using microelectrodes and a strain gage as previously described. 2 The following minor changes have been made in the original procedure and methods of recording. It has been found that an equilibration period of one hour instead of two hours is now satisfactory and provides stable preparations. The duration of the action potential was measured from the initiation of depolarization until the potential returns to within 20 mv. of the resting potential, eliminating fluctuations frequently present as the potential approaches the resting Received for publication August 6, 1958. 131 value. Since the depolarization time is very short, the average rate of repolarization can be calculated by dividing the amplitude of the action potential minus 20 mv. by the action potential duration. The area of the action potential was measured with a polar planimeter on an enlarged tracing of the record. That part of the total area was measured which was bounded by the rising and falling potential and a line at 20 mv. depolarization from the base line. It is assumed that the effect of depolarization on the contractile systems is negligible until the depolarization reaches a minimum of 20 mv. and the area here expressed would be one possible measure of the magnitude of the effective action potential. It is also possible that once a critical level of depolarization is achieved, further change in potential is without additional effect on the contractility, in which case the action potential duration would perhaps be a more reliable criterion of effectiveness. Solutions of the inhib...

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The Action of Iodoacetate on the Electrical and Mechanical Activities of the Isolated Perfused Frog Heart 1

Cited by 13 publications

References 12 publications

Influence of Glucose on the Transmembrane Action Potential of Guinea-Pig Papillary Muscle

Influence of Glucose on the Transmembrane Action Potential of Guinea-Pig Papillary Muscle

Influence of sodium ions on the membrane potential of the sino‐atrial node in response to sympathetic nerve stimulation

Effects of Enzyme Inhibitors on the Contractility and Membrane Potentials of the Rat Atrium

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