Biomaterial Database

Inhibition of the sodium pump in guinea-pig ventricular muscle by dihydro-ouabain: effects of external potassium and sodium. 1983

J Daut

The inhibition of the electrogenic pump current in quiescent guinea-pig ventricular muscle by dihydro-ouabain (DHO) was studied with the three-micro-electrode voltage-clamp technique described previously (Daut, 1982c). From dose-response curves of the drug-induced current change (ID) the equilibrium dissociation constant of the binding of DHO to the Na-K pump (KD) and the electrogenic pump current flowing in the steady state (Ip) were inferred (Daut & Rüdel, 1982b). The external K concentration ([K]o) was varied between 2 and 4.5 mM (substituted by Na). KD was found to increase with increasing [K]o. A plot of log KD versus log [K]o gave a straight line with a slope of about 1.5. The time constants of the onset (tau on) and decay (tau off) of ID are supposed to represent the chemical kinetics of binding and unbinding of the drug (Daut & Rüdel, 1981, 1982b). Tau on was found to be inversely related to [K]o whereas tau off was found to be independent of [K]o. Ip was found to be independent of [K]o. This was interpreted to indicate that in the steady state Ip is mainly determined by the passive influx of Na into the cell, which may be relatively insensitive to small changes in [K]o. The effects of [K]o on the drug-induced current change are consistent with competitive inhibition of the binding of DHO to the Na-K pump. It is suggested that K ions and cardiac glycosides compete for extracellular binding sites on the same conformation of the Na-K pump. The external Na concentration ([Na]o) was varied between 147 and 49 mM (substituted by choline or Tris). Reduction of [Na]o produced a proportional decrease of Ip. This may be a consequence of the accompanying reduction of passive Na influx and the resulting decrease in intracellular Na activity (alpha iNa). Reduction of [Na]o markedly increased KD. This effect may be mediated by competition between Na and K at the K-loading sites of the pump and/or by separate modulatory Na-binding sites. It is concluded that the well known effects of external Na and K on the positive inotropic action of cardiac glycosides can be fully accounted for by the marked changes in the apparent binding affinity of the drug reported here.

UI	MeSH Term	Description	Entries
D007473	Ion Channels	Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.	Membrane Channels,Ion Channel,Ionic Channel,Ionic Channels,Membrane Channel,Channel, Ion,Channel, Ionic,Channel, Membrane,Channels, Ion,Channels, Ionic,Channels, Membrane
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
D011188	Potassium	An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
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
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
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
D012964	Sodium	A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.	Sodium Ion Level,Sodium-23,Ion Level, Sodium,Level, Sodium Ion,Sodium 23
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor