Na+/K+ ATPase pump

Figure 41-13. Stoichiometry of the Na+-K ATPase pump. This pump moves three Na ions from inside the cell to the outside and brings two K+ ions from the outside to the inside for every molecule of ATP hydrolyzed to ADP by the membrane-associated ATPase. Ouabain and other cardiac glycosides inhibit this pump by acting on the extracellular surface of the membrane. (Courtesy of R Post.)...

The mechanism of uptake and retention of the mono-cationic 99mTc complexes in the myocardium - or other tissues - has not been fully resolved. Most of the mechanistic studies have been conducted with 99mTc (MIBI)6f and "mTc-diphosphine complexes. It has been shown that these mono-cationic complexes are not taken up in myocytes via the Na+/K+-ATPase pump as is 201T1+ [41]. Instead, these cationic tracers are localized and retained in cellular membranes, including mitochondrial membranes [41]. 

Explain the role of the Na+-K+ ATPase pump in this process... 

Aldosterone acts on the distal tubule of the nephron to increase sodium reabsorption. The mechanism of action involves an increase in the number of sodium-permeable channels on the luminal surface of the distal tubule and an increase in the activity of the Na+-K+ ATPase pump on the basilar surface of the tubule. Sodium diffuses down its concentration gradient out of the lumen and into the tubular cells. The pump then actively removes the sodium from cells of the distal tubule and into the extracellular fluid so that it may diffuse into the surrounding capillaries and return to the circulation. Due to its osmotic effects, the retention of sodium is accompanied by the retention of water. In other words, wherever sodium goes, water follows. As a result, aldosterone is very important in regulation of blood volume and blood pressure. The retention of sodium and water expands the blood volume and, consequently, increases mean arterial pressure. 

An essential requirement for diffusion of Na+ ions is the creation of a concentration gradient for sodium between the filtrate and intracellular fluid of the epithelial cells. This is accomplished by the active transport ofNa+ ions through the basolateral membrane of the epithelial cells (see Figure 19.4). Sodium is moved across this basolateral membrane and into the interstitial fluid surrounding the tubule by the Na+, K+-ATPase pump. As a result, the concentration of Na+ ions within the epithelial cells is reduced, facilitating the diffusion of Na+ ions into the cells across the luminal membrane. Potassium ions transported into the epithelial cells as a result of this pump diffuse back into the interstitial fluid (proximal tubule and Loop of Henle) or into the tubular lumen for excretion in the urine (distal tubule and collecting duct). 

T1, as the thallous ion (Tl+), has been used for imaging heart function under stress and rest conditions since about 1975. The thallous ion distributes in viable heart muscle as a potassium ion mimic, through the Na+-K+ ATPase pump. Clinical images with 201T1 show the infarcted regions of the heart as cold spots or without radioactivity. 2 T1 decays by electron capture with a... 

Geroski DH, Edelhauser HF. Quantitation of Na/K ATPase pump sites in the rabbit corneal endothelium. Invest Ophthalmol Vis Sci 25 1056-1060 (1984). 

Lithium is closely related to sodium in its properties. It can substitute for sodium in generating action potentials and in Na + -Na+ exchange across the membrane. It inhibits the latter process that is, Li+-Na+ exchange is gradually slowed after lithium is introduced into the body. At therapeutic concentrations (around 1 mmol/L), it does not significantly affect the Na + -Ca2+ exchanger or the Na +, K+ ATPase pump. 

The depletion of GSH and NADPH will allow the oxidation of protein sulfydryl groups, which may be an important step in the toxicity. Thus, GSH and protein sulfydryl groups, such as those on Ca2+-transporting proteins, are important for the maintenance of intracellular calcium homeostasis. Thus, paracetamol and NAPQI cause an increase in cytosolic calcium, and paracetamol inhibits the Na+/K+ ATPase pump in isolated hepatocytes. 

Amino acids, dipeptides, and some tripeptides are transported from the lumen of the intestine through the membrane of the brush border of the mucosal cells and into the cytoplasm, where the peptides are hydrolyzed to amino acids. Transport of peptides and amino acids is active and analogous to glucose transport i.e., they are transported, together with Na+, across the gut-cell membrane by specific transport proteins called Na+ symports. Between the gut lumen and the cytoplasm of the cell there is a concentration gradient of Na+ that is maintained by Na+/K+ ATPase at the base of the cell adjacent to the blood capillaries this Na+/K ATPase pumps Na+ from the cell into the blood. 

Blockade of potassium, sodium, calcium channels, P-adrenergic receptor sites, and the Na /K -ATPase pump change the ECG and may give an indication of the type of poisoning present in the tissue (Delk et al, 2007). 

Inhibition of the Na" /K -ATPase pump results in [K ]o and intercellular [Na" "] increases in turn increasing the intracellular calcium concentrations. 

The sodium—calcium exchanger in the plasma membrane of an animal cell is an antiporter that uses the electrochemical gradient of Na+ to pump Ca2+ out of the cell. Three Na+ ions enter the cell for each ion that is extruded. The cost of transport by this exchanger is paid by the Na+-K+- ATPase pump, which generates the requisite sodium gradient. 

Acute digoxin poisoning causes initial nausea and vomiting and hyperkalaemia because inhibition of the Na, K" -ATPase pump prevents intracellular accumulation of potassium. The ECG changes (see Table 24.1) of prolonged use of digoxin may be absent. There may be exaggerated sinus arrhythmia, bradycardia and ectopic rhythms with or without heart block. 

Blot-Chabaud, M., Warrstok, F., Bon valet, J.-P., and Farman, N. (1990). Cell sodium induced recruitment of Na -K -ATPase pumps in rabbit cortical collecting tubules is aldosterone-dependent. J. Biol. Oiem. 265, 11676-11681. 

In LLC-PKj cells gentamicin induces membrane damage as shown by the loss of specific membrane enzymes (y-glutamyl transpeptidase, alkaline phosphatase and aminopeptidase), a decrease of the lysosomal enzyme N-acetyl-P-D-glucosaminidase, an inhibition of apical Na -dependent glucose transporter and the basolateral Na-K-ATPase pump as well as a decrease in dome formation [141, 142]. Furthermore gentamicin results in a dose dependent decrease in intracellular ATP and cAMP [142]. 

MOA Digoxin (cardiac glycoside) is a positive inotropic agent that inhibits the Na+/K+ ATPase pump. Inhibition of the pump causes an increase in intracellular sodium that allows the Na+/Ca exchanger to increase intracellular calcium. The heart is then able to use the increased intracellular calcium to increase contractility. 

Martinez-Maldonado Cordova 1990, Rose 1989, 1991, Wilcox 1991). In the absence of a loop diuretic, sodium ions transported into the cell are translocated into the peritubular capillary by the action of the Na, K -ATPase pump. Chloride ions are translocated out of the cell by two pathways a selective chloride channel and an electroneutral K, Cr-cotransporter. These processes maintain low intracellular sodium and chloride ion concentrations and favor continued entry of sodium and chloride from the tubular lumen. In contrast, potassium ion concentrations in the tubular fluid and within the cell are lower and higher, respectively, compared with sodium and chloride. Although these potassium ion concentrations would seem to inhibit the action of the Na, K, 2Cr-cotrans-porter, this problem is overcome by the recycling of much of the reabsorbed potassium (that does... 

In the resting stale (dark), rod and cone membranes exhibit a steady electrical current. The membrane allows sodium ions to enter freely through. specific channels. A Na /K -ATPase pump maintains the ion gradient. The closing of the pores hyperpolarizcs the membrane and initiates the neuronal response. 

Bromethalin is an uncoupler of oxidative phosphorylation in mitochondria in cells of the central nervous system. Uncoupling leads to a decreased cellular ATP production and failure of the Na, K + -ATPase pumps, which in turn leads to sodium retention and a loss of ability to maintain osmotic control. The outcome is a buildup of cerebrospinal fluid and vacuolization of myelin. The resulting edema and high intracranial pressures cause damage to nerve axons, inhibiting neural transmission, and leads to paralysis, convulsions, and, ultimately, death. 

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