The actions of ouabain on intercellular coupling and conduction velocity in mammalian ventricular muscle. 1977

R Weingart

1. The effects of ouabain on the electrical coupling between cells and the conduction velocity, theta, were studied in ventricular muscle preparations from calf and cow hearts using a silicon-oil-chamber. 2. After 90 min of exposure to 2 X 10(-6) M ouabain, an increase of the inside longitudinal resistance, Ri, from 420 omega cm to 1032 omega CM was observed. Assuming a constant myoplasmic resistivity this presumably reflects a reduced electrical coupling between myocardial cells. 3. Concomitantly, theta was decreased from 50-3 to 29-4 cm/sec. This change could be explained by the observed alterations in the maximal rate of rise of the action potential, (dV/dt)max, the amplitude of the action potential Vp, the membrane capacity Cf, and the sum, respectively, of the inside and outside longitudinal resistance per unit distance (ri + ro). Quantitatively, about 60% of the decrease of theta could be accounted for by the experimentally determined increase of Ri. 4. Time course studies revealed a biphasic action of ouabain on Ri. An early dose-dependent drop in Ri, equivalent to an improvement of the intercellular coupling, was followed by a delayed massive increase in Ri, whose onset and magnitude were also concentration-dependent. 5. The delayed increase in Ri was associated with an increase of the diastolic tension. Toxic ouabain doses (2 X 10(-6) M) produced irreversible changes on both parameters, whereas thereapeutic doses (less than 5 X 10(-7) M) affected neither of them. Reversible effects on both parameters were observed at an intermediate drug concentration (10(-6) M). 6. The strong correlation between decoupling and contracture is consistent with the idea that the intracellular Ca concentration, [Ca]i, is involved in the control of the nexal conductance. This is supported by the finding that increasing the extracellular Ca concentration, [Ca]o, accelerated the ouabain-induced decoupling, whereas reducing [Ca]o retarded it. 7. If anything, the contracture slightly preceded the increase in Ri. From this it is concluded that the threshold [Ca]i for the electrical decoupling between cells must be somewhat larger than the threshold level for the tension activation. 8. The delayed increase in Ri is compatible with an inhibition of the Na pump which according to the Na-lag hypothesis predicts an increase of [Ca]i secondary to a Na-accumulation. The early drop in Ri can either be explained by a stimulation of the Na pump, or by a non-monotonic relationship between Ri and [Ca]i.

UI MeSH Term Description Entries
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D010042 Ouabain A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like DIGITALIS. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-EXCHANGING ATPASE. Acocantherin,G-Strophanthin,Acolongifloroside K,G Strophanthin
D002417 Cattle Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor. Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004553 Electric Conductivity The ability of a substrate to allow the passage of ELECTRONS. Electrical Conductivity,Conductivity, Electric,Conductivity, Electrical
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts
D006352 Heart Ventricles The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation. Cardiac Ventricle,Cardiac Ventricles,Heart Ventricle,Left Ventricle,Right Ventricle,Left Ventricles,Right Ventricles,Ventricle, Cardiac,Ventricle, Heart,Ventricle, Left,Ventricle, Right,Ventricles, Cardiac,Ventricles, Heart,Ventricles, Left,Ventricles, Right
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
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