• It acts by inhibiting the Na/K-ATPase, also known as the sodium-potassium ion pump. (wikipedia.org)
  • Ouabain is a cardiac glycoside that acts by inhibiting the Na+/K+-ATPase sodium-potassium ion pump (but it is not selective). (wikipedia.org)
  • Therefore, the decrease in the concentration gradient of sodium into the cell which occurs when the Na/K-ATPase is inhibited reduces the ability of the NCX to function. (wikipedia.org)
  • Electroporation-mediated in vivo gene delivery of the Na+/K+-ATPase pump reduced lung injury in a mouse model of lung contusion. (nih.gov)
  • Embryotrophic factor-3 from human oviductal cells enhances proliferation, suppresses apoptosis and stimulates the expression of the beta1 subunit of sodium-potassium ATPase in mouse embryos. (nih.gov)
  • The pump that maintains these gradients is an ATPase that is activated by Na+ and K+ (Na+-K+ATPase). (maxanim.com)
  • Ouabain or digitalis inhibits this ATPase by binding to the extracellular domain. (maxanim.com)
  • Inhibition of the ATPase by ouabain can be antagonized by extracellular K+. (maxanim.com)
  • These findings assign novel, 'profound' and early lethal phenotypes of developmental and epileptic encephalopathies and polymicrogyria to the phenotypic spectrum associated with heterozygous ATP1A2/A3 mutations and indicate that severely impaired NKA pump function can disrupt brain morphogenesis.Sorcin activates the plasma membrane Ca2+-ATPase (PMCA) activity and prevents the inhibition of the pump by amyloid-β peptide (Aβ1-42) and tau. (kunstatelier-kd.de)
  • 1][2] The Na+ K+ ATPase pumps 3 Na+ out of the cell and 2K+ that into the cell, for every single ATP consumed. (kunstatelier-kd.de)
  • In study I we showed a mechanism of ouabain-dependent regulation of the NMDA receptor, one of the most important receptors in the nervous system, via binding with Na + ,K + -ATPase. (kth.se)
  • In study II we investigated a different aspect of Na + ,K + -ATPase functioning - to look at how binding of ouabain to Na + ,K + -ATPase activates a number of signaling cascades by looking at the phosphoproteome status of the cells. (kth.se)
  • In the on-going study we showed that Na + ,K + -ATPase can oligomerize and that this effect is triggered by ouabain binding to the Na + ,K + -ATPase. (kth.se)
  • These bind to a site on the cell membrane, producing reversible inhibition of the sodium (Na + )-potassium (K + )-adenosine triphosphatase (ATPase) pump. (medscape.com)
  • Inhibition of Na + -K + -ATPase in skeletal muscle results in increased extracellular potassium and contributes to hyperkalemia. (medscape.com)
  • Like other cardiac glycosides, these toxins exert their effects by inhibiting the ATPase activity of a complex of transmembrane proteins that form the sodium potassium ATPase pump, (Na+/K+-ATPase). (blogspot.com)
  • Na(+),K(+) ATPase is an essential ion pump involved in regulating ionic concentrations within epithelial cells. (mdc-berlin.de)
  • Functional tests and pharmacological inhibition experiments demonstrate that Na(+),K(+) ATPase activity is positively regulated via an N-terminal phosphorylation site that is necessary for correct heart morphogenesis to occur, and that maintenance of ZO-1 junction belts requires ion pump activity. (mdc-berlin.de)
  • 15 mM K+ evoked dilation sensitive to inhibition of K(IR) (30 microM Ba2+) and Na+/K+-ATPase (10 microM ouabain), whereas these blockers did not affect ACh-mediated dilations. (ox.ac.uk)
  • It is a cardioactive derivative of lanatoside A or of digitoxin used for fast digitalization in congestive heart failure.Acetyldigitoxin binds to a site on the extracellular aspect of the α-subunit of the Na + /K + ATPase pump in the membranes of heart cells (myocytes). (hmdb.ca)
  • The amount of potassium pumped into the cells at various concentrations of extracellular potassium has been calculated. (harvard.edu)
  • Building on these findings, the lab addressed the coordinated and concerted control of extracellular potassium by skeletal muscle, kidney and gut in response to altered metabolic and electrolyte demands and have begun to use these findings to address the mechanisms responsible for the cardiovascular benefit of raising dietary K/Na ratio. (usc.edu)
  • This increase in intracellular sodium reduces the activity of the sodium-calcium exchanger (NCX), which pumps one calcium ion out of the cell and three sodium ions into the cell down their concentration gradient. (wikipedia.org)
  • Ions , such as sodium (Na + ) and chloride (Cl - ), have an even more difficult time going through the membrane than glucose . (visionlearning.com)
  • This gene encodes an integral membrane protein that comprises a subunit of an ATP-metabolizing enzyme responsible for transporting sodium and potassium ions across the plasma membrane. (nih.gov)
  • The number of ions moving downhill via the pump per mole orthophosphate incorporated into ATP was the same as the stoichiometry for active transport, indicating the same efficiency for ATP splitting and ATP labelling. (le.ac.uk)
  • The sodium ion (Na + ) is the main determinant of the body fluid distribution, and transsarcolemmal Na + gradient is a key regulator of the various intracellular ions and metabolites. (biomedcentral.com)
  • Sodium-binding benzofuran isophthalate (SBFI), the most widely used Na + -sensitive fluorescent indicator provides spatial and temporal resolution of [Na + ] i with sufficient selectivity in the presence of physiological concentrations of other ions [ 11 ]. (biomedcentral.com)
  • This causes an increase in the level of sodium ions in the myocytes, which then leads to a rise in the level of calcium ions. (hmdb.ca)
  • Ouabain is a cardiac glycoside and in lower doses, can be used medically to treat hypotension and some arrhythmias. (wikipedia.org)
  • The change in ionic gradients caused by ouabain can also affect the membrane voltage of the cell and result in cardiac arrhythmias. (wikipedia.org)
  • Initially, her lab focused on regulation of the biosynthesis and assembly of sodium pump subunits and molecular mechanisms controlling sodium pump isoforms in kidney, cardiac and skeletal muscle by potassium, hormones, and other factors under normal conditions and during human heart failure. (usc.edu)
  • However, digitoxin, digoxin and several other cardiac glycosides, such as ouabain, are known to have steep dose-response curves, i.e. minute increases in the dosage of these drugs can make the difference between an ineffective dose and a fatal one. (blogspot.com)
  • Intracellular sodium ([Na + ] i ) kinetics are involved in cardiac diseases including ischemia, heart failure, and hypertrophy. (biomedcentral.com)
  • Cardiac glycosides are found in a diverse group of plants including Digitalis purpurea and Digitalis lanata (foxgloves), Nerium oleander (common oleander), Thevetia peruviana (yellow oleander), Convallaria majalis (lily of the valley), Urginea maritima and Urginea indica (squill), Strophanthus gratus (ouabain), Apocynum cannabinum (dogbane), and Cheiranthus cheiri (wallflower). (medscape.com)
  • The Ca2+-inhibition of K-pNNPase was accompanied by increased sensitivity of the enzyme to ouabain. (mcmaster.ca)
  • The proposed mechanism is the following: inhibition of the Na + /K + pump leads to increased Na + levels, which in turn slows down the extrusion of Ca 2+ via the Na + /Ca 2+ exchange pump. (hmdb.ca)
  • [1-3] Because of the hypnotic effects of these agents, attention has focused mainly on the central nervous system, and several studies have reported that halothane exposure depressed voltage-gated sodium (Na) channels and potassium (K) channels. (asahq.org)
  • Part One describes chemical studies with erythrocyte ghosts to test whether incorporation of radioactive orthophosphate (32Pi) into adenosine triphosphate (ATP) was associated with concentration gradients of sodium and potassium across the membrane. (le.ac.uk)
  • In Part Two, movements of sodium and potassium down concentration gradients are described. (le.ac.uk)
  • It creates sodium and potassium gradients which are fundamental for the membrane potential and sodium-dependent secondary active transport. (kth.se)
  • Further, ouabain-sensitive potassium efflux was dependent on external sodium, and ouabain-sensitive sodium influx was abolished when potassium was added to the external medium. (le.ac.uk)
  • Methods: We used formamide-induced detubulation of mouse ventricular myocytes to investigate differential functional distribution and regulation by PKA of α 1 and α 2 in T-tubule versus SSL membranes by measuring NKA current (I pump ) and NKA-mediated Na + efflux (- d[Na] i /dt). (uky.edu)
  • Mutations in four genes have been identified in familial hemiplegic migraine (FHM), from which CACNA1A (FHM type 1) and SCN1A (FHM type 3) code for neuronal voltage-gated calcium or sodium channels, respectively, while ATP1A2 (FHM type 2) encodes the α 2 isoform of the Na + ,K + -ATPase's catalytic subunit, thus classifying FHM primarily as an ion channel/ion transporter pathology. (frontiersin.org)
  • These transporters can be active (pumps) or passive (channels) and are sometimes regulated by gates. (visionlearning.com)
  • Potassium (K + ) channels have an important role in HCC, including regulating the proliferation, migration, invasion and drug resistance of HCC cells. (spandidos-publications.com)
  • Huang X and Jan LY: Targeting potassium channels in cancer. (spandidos-publications.com)
  • Teisseyre A, Gąsiorowska J and Michalak K: Voltage-gated potassium channels Kv1.3-potentially new molecular target in cancer diagnostics and therapy. (spandidos-publications.com)
  • Kuang Q, Purhonen P and Hebert H: Structure of potassium channels. (spandidos-publications.com)
  • Comes N, Serrano-Albarrás A, Capera J, Serrano-Novillo C, Condom E, Ramón Y Cajal S, Ferreres JC and Felipe A: Involvement of potassium channels in the progression of cancer to a more malignant phenotype. (spandidos-publications.com)
  • Na enters the cells through amiloride-sensitive Na channels or Na cotransporters and is extruded by a Na pump. (asahq.org)
  • Exposure of epithelial type II cells to halothane reduced the activity of sodium, potassium-adenosine triphosphatase, and amiloride-sensitive Na channels, whereas Na cotransporters were unchanged. (asahq.org)
  • They discovered that changes in blood pressure, or alterations in Angiotensin II, provoke rapid trafficking of renal sodium transporters between membrane domains, associated with phosphorylation and pool size regulation. (usc.edu)
  • 7 Cheng J T, Kahn T, Kaji D M. Mechanism of alterations in sodium-potassium pump of erythrocytes from patients with chronic renal failure. (thieme-connect.com)
  • Ouabain can be found in the roots, stems, leaves, and seeds of the Acokanthera schimperi and Strophanthus gratus plants, both of which are native to eastern Africa. (wikipedia.org)
  • Seeds of Strophanthus gratus provide two Active glycoside - STROPHANTHUS-G and OUABAIN, While seeds of strophanthus kombe yield primarily STROPHANTHIN-K. (pharmanotes.org)
  • The plasma membrane-enriched fraction isolated from smooth muscle of rat gastric fundus was found to contain a substantial level of potassium-stimulated p-nitrophenylphosphatase activity (K-pNPPase), and its subcellular distribution closely resembled that of other plasma membrane enzyme markers. (mcmaster.ca)
  • Ouabain is eliminated by renal excretion, largely unchanged. (wikipedia.org)
  • The McDonough laboratory has especially focused on renal mechanisms responsible for regulation of sodium and potassium balance as well as blood pressure. (usc.edu)
  • Using the transporter profiling approach, Dr. McDonough and her colleagues have defined how stimuli such as dietary salts, Ang II, kidney injury, and immune cytokines increase renal sodium transport in a region specific manner along the nephron and how resultant hypertension provokes intrarenal responses to decrease sodium reabsorption (via pressure natriuresis), a response that defines the blood pressure set point in the kidney. (usc.edu)
  • A number of analytical techniques led to the conclusion that this circulating molecule was ouabain and that humans were producing it as an endogenous hormone. (wikipedia.org)
  • An estimate of sodium-potassium pump activity and the number of pump sites in the smooth muscle of the guinea-pig taenia coli, using (3H)ouabain. (harvard.edu)
  • An equation for membrane voltage is derived that takes into account the electrogenicity of the Na/K pump and is valid dynamically, as well as in the steady state. (shwi.org)
  • The results emphasize the role of the pump and membrane voltage in lowering internal Cl− concentration, thus making osmotic room for vital substances that must be sequestered in the cell. (shwi.org)
  • The decrease in sodium, potassium-adenosine triphosphatase activity was maximal for 30 min of exposure and reached 50, 42, and 56% for halothane concentrations of 1, 2, and 4%, respectively, and did not change for longer exposure times. (asahq.org)
  • It has a second role in the cell as a receptor that by binding chemicals from the cardiotonic steroids family, the most knowledgeable of them is ouabain, triggers various signaling pathways in the cell which regulate gene activation, proliferation, apoptosis, etc. (kth.se)
  • Mutations in the genes encoding a calcium channel (Ca V 1.1) and a sodium channel (Na V 1.4) have been identified in HypoPP families. (jci.org)
  • Nitroprusside inhibited L-type calcium currents, transient outward currents and transient inward current, but increased delayed rectified potassium currents. (biomedcentral.com)
  • 14 Kaji D M, Thakkar U, Kan T. Glucocorticoid-induced alterations in sodium-potassium pump of the human erythrocyte. (thieme-connect.com)
  • 3 Beno D J. Amiloride: a molecular probe of sodium transport in tissues and cells. (thieme-connect.com)
  • We performed a molecular and cellular study to describe how mutations affects protein structure and function and found that this mutation converts the ion pump to a nonspecific leak channel. (kth.se)
  • α 1 and α 2 subunits demonstrate distinct ouabain affinities (105 ± 6 and 0.3 ± 0.1 μmol/L respectively) but similar affinity for intracellular Na + (K 1/2 Na + of 16.6 ± 0.8 and 16.7±2.6 mmol/L respectively). (uky.edu)
  • Additional labelling depended on the ionic composition of ghosts and medium, and was prevented by ouabain. (le.ac.uk)
  • The action potential and ionic currents were investigated in isolated single canine PV cardiomyocytes before and after sodium nitroprusside (80 μM,) using the whole-cell patch clamp technique. (biomedcentral.com)
  • previous paper presented the typical dependences for the cells with high MP and high intracellular K/Na ratio, for the cells with low MP and high K/Na ratio (high potassium erythrocytes) and for the low-MP and low-K/Na-ratio cells (low-potassium erythrocytes of some carnivores and ruminants) ( Vereninov et al. (researchgate.net)
  • And a common aliment, heartburn, is treated with medicine that slows down the rate at which protons are pumped across cell membranes into the stomach. (visionlearning.com)
  • Total I pump density was ∼ 60% higher in T-tubule (1.94 pA/pF, derived) vs. SSL membranes. (uky.edu)
  • BYU cell biology and physiology professor Jeff Edwards' research findings validate those new year's resolutions to get the heart pumping and exercise more. (kunstatelier-kd.de)
  • Reversal of the sodium pump in human red cells. (le.ac.uk)
  • In the absence of external potassium, cells lost potassium and gained sodium in a way partly sensitive to ouabain. (le.ac.uk)
  • 12 Joiner C H, Lauf P K. Ouabain binding and potassium transport in young and old populations of human red cells. (thieme-connect.com)
  • In addition to synthesizing surfactant, alveolar type II cells actively transport sodium (Na) from the alveolar space to the interstitium. (asahq.org)
  • Sodium, potassium-adenosine triphosphatase, and amiloride-sensitive Na channel activities are impaired by halothane in alveolar type II cells in vitro. (asahq.org)
  • The kinetic profile of K-pNPPase and its sensitivity toward ouabain and vanadate confirmed the identification of this activity with the partial reaction of the sodium pump. (mcmaster.ca)
  • The specific activity of K-pNPPase and its sensitivity to ouabain was significantly increased in the presence of saponin, indicating that part of this activity is latent when assayed on native membrane preparation. (mcmaster.ca)
  • A large volume infusion pump that continuously or intermittently delivers fluids, medications, blood and blood products to adult, pediatric or neonatal patients. (kunstatelier-kd.de)
  • Critically, the primary observations concerning the identification of ouabain in mammals were repeated and confirmed using a variety of tissue sources on three different continents with advanced analytical methods as summarized elsewhere Despite widespread analytical confirmation, some questioned whether or not this endogenous substance is ouabain. (wikipedia.org)
  • found that the kinetics of the disturbance of cell ion and water balance caused by blocking the Na +/ K + pump when the intracellular K + /Na + ratio is highly changed and even reversed can be predicted sufficiently well by calculation with the invariant parameters ( Vereninov et al. (researchgate.net)
  • In 1991, a specific high affinity sodium pump inhibitor indistinguishable from ouabain was first discovered in the human circulation and proposed as one of the potential mediators of long term blood pressure and the enhanced salt excretion following salt and volume loading. (wikipedia.org)
  • The wave velocity was accelerated at low frequencies by increased Mg 2+ concentrations, by ouabain and by curare, and the same substances decreased the wave velocity at high frequencies. (biologists.com)
  • Archaeological and anthropological studies show that the diets of hunter-gatherers during the Paleolithic period and the diets of present-day traditional societies outside the dominant culture have, with few exceptions, had high levels of potassium and very low levels of sodium (Denton, 1982). (nationalacademies.org)
  • An overdose of ouabain can be detected by the presence of the following symptoms: rapid twitching of the neck and chest musculature, respiratory distress, increased and irregular heartbeat, rise in blood pressure, convulsions, wheezing, clicking, and gasping rattling. (wikipedia.org)
  • Yet another argument against the existence of endogenous ouabain was the lack of effect of rostafuroxin (a first generation ouabain receptor antagonist) on blood pressure in an unselected population of hypertensive patients. (wikipedia.org)
  • These projects have engaged the McDonough lab with expert collaborators across the USA and around the world and attracted attention to the important role of the kidney in balancing the intertwined homeostasis of sodium, potassium and blood pressure. (usc.edu)
  • The results show that a part of the incorporation of orthophosphate into ATP appeared to occur by reversal of the sodium pump. (le.ac.uk)
  • Results: I pump is composed of 88% α 1 -mediated I pump (Iα 1 ) and 12% α 2 -mediated I pump (Iα 2 ). (uky.edu)
  • In France and Germany, however, intravenous ouabain has a long history in the treatment of heart failure, and some continue to advocate its use intravenously and orally in angina pectoris and myocardial infarction despite its poor and variable absorption. (wikipedia.org)
  • Congestive heart failure (CHF), or heart failure, is a condition in which the heart is unable to pump sufficient blood to meet the metabolic demand of the body and also unable to receive it back because every time after a systole. (pharmanotes.org)
  • Ejection Fraction (EF) is the percentage of blood that is pumped out of your heart during each beat. (pharmanotes.org)
  • Purpose: To evaluate the effect of ATP-sensitive potassium channel openers cromakalim prodrug 1 (CKLP1) and diazoxide on IOP in three independent mouse models of ocular hypertension. (bvsalud.org)
  • Research into pain relievers provided insight into the most important and universal transporter in the human body, the sodium-potassium pump. (visionlearning.com)
  • Sodium, potassium, and their attendant anions are important components of all body fluids. (nationalacademies.org)
  • Conclusions: ATP-sensitive potassium channel openers CKLP1 and diazoxide effectively decreased the IOP in ocular hypertensive animal models by decreasing the episcleral venous pressure, supporting a potential therapeutic application of these agents in ocular hypertension and glaucoma. (bvsalud.org)