What are the side effects of ouabain?Asked by: Carli Monahan
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Hereof, What does ouabain do to the heart?
Increased intracellular concentrations of calcium may promote activation of contractile proteins (e.g., actin, myosin). Ouabain also acts on the electrical activity of the heart, increasing the slope of phase 4 depolarization, shortening the action potential duration, and decreasing the maximal diastolic potential.
Also Know, What does ouabain do to a neuron?. Ouabain is well-known to prolong depolarization of neurons leading to osmolysis or calcium necrosis in brain tissues . Upon ouabain binding, the Na, K-ATPase initiates a series of reactions that include interaction with neighboring proteins in what has been described as the Na, K-ATPase signal [9, 10].
In respect to this, Why is ouabain a lethal poison?
The elevated intracellular Na+ reduces the activity of the Na+/Ca2+ exchanger (NCX), resulting in abnormal Ca2+ fluctuations which is associated with cardiac arrhythmias. Ouabain is a highly toxic compound (LD50 2.2 mg/kg, intravenously administration to mouse) and can cause symptoms such like vomiting and convulsion.
How is ouabain used to treat CHF?
Ouabain prevents pathological cardiac hypertrophy and heart failure through activation of phosphoinositide 3-kinase α in mouse. Cell Biosci.
Ouabain is a cardiac glycoside that inhibits ATP-dependent sodium-potassium exchange across cell membranes. The binding of ouabain to the sodium-potassium pump (also called Na+/K+ ATPase) prevents the conformational changes necessary for its proper function.
If this pump stops working (as occurs under anoxic conditions when ATP is lost), or if the activity of the pump is inhibited (as occurs with cardiac glycosides such as digoxin), Na+ accumulates within the cell and intracellular K+ falls.
Ouabain, a new steroid hormone of adrenal gland and hypothalamus.
Our results are consistent with those of others who suggest that ouabain causes an increase in transient inward current" and a decrease in iw . These changes decrease membrane potential, increase the slope of phase 4, and may activate a slow inward current and induce afterdepolarizations.
Our results suggest that ouabain binds at two sites along the ion permeation pathway of the Na+/K+ ATPase. The external site (low apparent affinity) occupies the same region as previous structural findings. The high apparent affinity site is, however, slightly deeper toward the intracellular end of the protein.
In cardiac cells, ouabain increases intracellular Ca2+ concentration and cardiac muscle contractility by inhibiting Na-K-ATPase activity, thus stimulating Na/Ca exchange (4). In some cells, however, ouabain at very low (pM to nM) concentrations increases Na-K-ATPase activity (23).
ATPases are a group of enzymes that catalyze the hydrolysis of a phosphate bond in adenosine triphosphate (ATP) to form adenosine diphosphate (ADP). They harness the energy released from the breakdown of the phosphate bond and utilize it to perform other cellular reactions.
: a poisonous glycoside C29H44O12 obtained from several African shrubs or trees (genera Strophanthus and Acokanthera) of the dogbane family and used medically like digitalis and in Africa as an arrow poison.
Cardiac glycosides are a class of organic compounds that increase the output force of the heart and increase its rate of contractions by acting on the cellular sodium-potassium ATPase pump.
In 1882, ouabain was first isolated from the plant by the French chemist Léon-Albert Arnaud as an amorphous substance, which he identified as a glycoside. Ouabain was seen as a possible treatment for certain cardiac conditions.
Digitalis medicines strengthen the force of the heartbeat by increasing the amount of calcium in the heart's cells. (Calcium stimulates the heartbeat.) When the medicine reaches the heart muscle, it binds to sodium and potassium receptors.
High doses of ouabain cause lymphoma cell death [106,107]; however, it stimulates proliferation of some lymphocytic leukemia cells . Ouabain prevents the growth of medulloblastoma and glioblastoma cells and tumors [109,110,111].
Deslanoside inhibits the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium and calcium concentrations .
physiological response of photoreceptors. The depolarization is brought about by the entry of sodium and calcium ions that results from the opening of membrane channels.
Cardiac glycosides are medicines for treating heart failure and certain irregular heartbeats. They are one of several classes of drugs used to treat the heart and related conditions. These drugs are a common cause of poisoning.
Mechanism of Action
Digoxin induces an increase in intracellular sodium that will drive an influx of calcium in the heart and cause an increase in contractility. Cardiac output increases with a subsequent decrease in ventricular filling pressures.
The Na+ K+ pump is an electrogenic transmembrane ATPase first discovered in 1957 and situated in the outer plasma membrane of the cells; on the cytosolic side.
The sodium-potassium pump is a vital enzyme found in all human cells which constantly maintains an optimal ion balance. This uses up a great deal of energy - about a fourth of the body's energy, the so-called ATP, is used to keep the pump going; in the brain the share is nearly 70%.
If equal amounts of Na+ and K+ were transported across the membrane by the pump, the net charge transfer would be zero; there would be no net flow of current and no effect on the membrane potential.
When the sodium-potassium- ATPase enzyme points into the cell, it has a high affinity for sodium ions and binds three of them, hydrolyzing ATP and changing shape. As the enzyme changes shape, it reorients itself towards the outside of the cell, and the three sodium ions are released.