Electromechanical studies on the inotropic effects of acetylstrophanthidin in ventricular muscle.
(1/42)
Three phases in the inotropic response of acetyl strophanthidin (AcS) on the electromechnical activity of the frog ventricular myocardium were identified and studied using a single sucrose voltage-clamp technique and other conventional electrophysiological methods. 2. the positive inotropic response of the drug was accompanied by a shift in tension-voltage relation, so that more tension developed with every depolarization step above the mechanical threshold (-50mV). Only at higher drug concentrations or with long exposure times did the mechanical threshold shift to more negative membrane potentials (-60 to-70 mV). 3. In tetrodotoxin-treated muscles AcS produced marked potentiation of twitch tension and an appropriate shift in the tension-voltage relation. 4. the positive inotropic response of the drug was not related to the magnitude of the direction of the fast or slow Na current. 5. in tetrodotoxin-treated ventricular strips the direction or the magnitude of the secondary inward current (ICa or INa) were not related to the inotropic effect of AcS. 6. AcS shortens the action potential markedly during the later stages of its positive inotropic response. When Ca2+ is omitted from the bathing solution AcS not only fails to shorten the action potential, but often prolongs it. 7. The shortening of the action potential in the presence of AcS is accompanied by an increase in the "instantaneous" membrane conductance both at rest and during the time course of the plateau. 8. The decline in the positive inotropic response of the drug was accompanied by the shortening of the action potential. Electrical or chemical prolongation of the action potential restored the full positive inotropic response if the membrane had not depolarized. 9. Membrane depolarization and the development of diastolic tension always occurred at later stages of drug action. Elevation of [Mg+2]degrees to 5 or 10 mM prevented or suppressed the membrane depolarization and the diastolic tension. 10. KCl-induced contractures were potentiated throughout the duration of drug exposure. The tonic component of the contracture tension was markedly elevated especially at later stages of drug action. 11. The experimental evidence suggests that no unitary mechanism could account for multiple actions of acetyl strophanthidin. However, the contributions of the Na pump, the Ca+2 sequestering system, and the K-efflux system to the various stages of drug action are discussed. (+info)
The effects of tension on acetylstrophanthidin-induced transient depolarizations and aftercontractions in canine myocardial and Purkinje tissues.
(2/42)
Transmembrane potentials and contractile activity were recorded from isolated canine Purkinje and ventricular muscle preparations exposed to acetylstrophantidin (AS) and subjected to a resting tension equal to 80% of that required to elicit peak developed tension. AS induced transient depolarizations (TD's) accompanied by aftercontractions in Purkinje tissue. AS also induced aftercontractions in 11 muscle preparations, and in seven of these the mechanical events were associated with TD's. Aftercontractions and TD's in both and the coupling intervals were directly related to the preceding basic cycle length (BCL). The amplitudes of aftercontractions and TD's reached a maximum at a coupling interval of 600-700 msec. Tension increased the amplitude of TD's in Purkinje tissue and promoted the appearance of TD's in muscle. TD's in muscle occasionally reached threshold in the presence of tension. The results of this study suggest that stretch or increased resting tension may promote the types of cardiac arrhythmias that are causally related to digitalis-induced TD's. The results are compatible with the hypothesis that TD's are caused either by a transmembrane influx of calcium or by an internal release of calcium ions. (+info)
Suppression of ouabain-induced atrial arrhythmias by carotid sinus stimulation.
(3/42)
In dogs anaesthetized with chloralose ectopic atrial arrhythmias were produced by subepicardial injection of ouabain. Stimulation of the right carotid sinus abruptly suppressed the ectopic arrhythmias. They returned on cessation of stimulation and sometimes already during the period of stimulation. It is suggested that in view of its response to carotid sinus stimulation the ouabain-induced arrhythmia resembles paroxysmal atrial tachycardia and that it is distinct from the aconitine-induced arrhythmia which on account of its response to vagal stimulation has been classified as atrial flutter. (+info)
Ouabain-induced ventricular tachycardia and its effect on the performance and metabolism of the dog heart.
(4/42)
At constant pressure work there was an increase in the oxygen consumption of the dog heartlung preparation after tachycardia due to auricular stimulation and a far greater increase in consumption after ouabain-induced ventricular tachycardia, as compared with control hearts beating at their own sinus rhythm. In neither condition was the increase in coronary flow greater than the spontaneous increase in the controls. It is suggested that an increase in oxygen demand, under certain circumstances, may be met primarily by an increased desaturation of coronary blood. "Therapeutic" doses of ouabain did not improve the mechanical efficiency of the preparation. "Toxic" doses of ouabain which gave rise to ventricular tachycardia did not decrease the phosphocreatine or labile nucleotide phosphorus content of the heart provided there was no hypoxia of the heart muscle. (+info)
SODIUM FLUXES IN DESHEATHED FROG SCIATIC NERVE.
(5/42)
Desheathed frog (R. pipiens) sciatic nerves were soaked in solutions that contained ouabain or NaN(3), in K-free solutions, or in K- and Ca-free solutions. Then, the nerves were allowed to recover in standard Ringer's solution. At various times during the soaking periods, some nerves were analyzed for Na and K, and estimates were made of the influx and efflux of Na(22). While a nerve was soaking in any one of the experimental solutions, the Na(22) influx was increased, the Na content was rising, and the K content was falling by an equivalent amount. The rate coefficient for Na(22) efflux was reduced by about 25 per cent by 0.05 mM ouabain and by about 50 per cent by 5 mM NaN(3). Potassium-free solutions had little effect on the rate coefficient. It was concluded that the efflux of Na from frog nerve is dependent on the metabolism, but not on the external concentration of K. The equimolar exchange that is characteristic of the net movements of Na and K in frog nerve may not be due to the presence of a tightly coupled Na-K exchange pump, but may represent a constraint imposed by the requirement for electroneutrality. (+info)
NUTRITION AND METABOLISM OF MARINE BACTERIA. XII. ION ACTIVATION OF ADENOSINE TRIPHOSPHATASE IN MEMBRANES OF MARINE BACTERIAL CELLS.
(6/42)
Drapeau, Gabriel R., (Macdonald College of McGill University, Quebec, Canada) and Robert A. MacLeod. Nutrition and metabolism of marine bacteria. XII. Ion activation of adenosine triphosphatase in membranes of marine bacterial cells. J. Bacteriol. 85:1413-1419. 1963.-Isolated membranes of two species of marine bacteria, a Pseudomonas and a Cytophaga, have been shown to possess adenosine triphosphatase activity. The optimal pH for enzyme action of both organisms was 8.8. The enzyme system was found to be capable of splitting inorganic o-phosphate from adenosine triphosphate (ATP), adenosine diphosphate, adenosine monophosphate, and inosine triphosphate but not from inorganic pyrophosphate. Mg(++) was required for enzyme activity; with the Pseudomonas species, the optimal Mg(++) to ATP ratio was 1:1. Ca(++) could not replace Mg(++). In the presence of the optimal concentration of Mg(++), the enzyme system was further stimulated, nonspecifically, by a number of different salts. Maximal activation was achieved at an ionic strength of 0.3 to 0.4. No evidence of an adenosine triphosphatase specifically activated by a combination of Na(+) and K(+) was obtained with either organism. No effect of ouabain on either the membrane adenosine triphosphatase activity or Na(+) transport by whole cells could be detected. The results suggest that the mechanism of ion regulation in marine bacterial cells is different from that in animal cells. (+info)
THE INTERACTION OF SOME STIMULANT AND DEPRESSANT DRUGS ON THE FROG HEART.
(7/42)
THE ACTIVITY OF FROG ISOLATED HEARTS WAS DEPRESSED BY ALTERING THE PERFUSING RINGER SOLUTION IN FIVE DIFFERENT WAYS: by reducing the calcium content, by increasing the potassium content, and by adding ether, thiopentone or acetylcholine. Depressed hearts were perfused with Ringer solution containing the following stimulant drugs: paullinia tannin, tannic acid, hydrogen peroxide, sodium oleate, sodium caprylate and ouabain. All these stimulant drugs had similar actions on hearts depressed by calcium lack, ether and thiopentone; hearts depressed by acetylcholine were, however, only weakly stimulated. Hearts depressed by potassium were readily stimulated by oleate, caprylate and paullinia tannin; ouabain and hydrogen peroxide had weak stimulant actions on hearts depressed by potassium, and tannic acid had a negative inotropic action. The differing actions on hearts depressed by potassium are probably related to differences in the degrees of fixation of the stimulant drugs. The mode of action of ouabain and the functional lesion in hearts depressed by narcotics are discussed. (+info)
THE ORIGIN OF THE SHORT-CIRCUIT CURRENT IN THE ISOLATED SKIN OF THE SOUTH AMERICAN FROG LEPTODACTYLUS OCELLATUS.
(8/42)
In isolated skins of Leptodactylus ocellatus the short-circuit current is smaller than the sodium net flux and this difference disappears when the skins are bathed in solutions in which the chloride ions have been replaced by sulfate or methylsulfate ions. There is a net movement of chloride ions from outside to inside of the skins in the short-circuit condition with chloride Ringer's solutions bathing the skins. The addition of ouabain to the inside solution markedly reduced not only sodium net flux but also the chloride net influx found. Copper ions added to the outside solutions produced a rise in short-circuit current, as well as the known increase in potential difference. In sodium-free Ringer's (sodium replaced by choline) the orientation of the potential difference across the skins was reversed, the inside being negative instead of positive. The results are interpreted as direct or indirect indications of the presence of a net transfer of chloride ions from outside to inside of these frog skins. (+info)