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 ventricular action potential is depicted in Fig. 6-2.2 Myocyte resting membrane potential is usually -70 to -90 mV, due to the action of the sodium-potassium adenosine triphosphatase (ATPase) pump, which maintains relatively high extracellular sodium concentrations and relatively low extracellular potassium concentrations. During each action potential cycle, the potential of the membrane increases to a threshold potential, usually -60 to -80 mV. When the membrane potential reaches this threshold, the fast sodium channels open, allowing sodium ions to rapidly enter the cell. This rapid influx of positive ions... 

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). 

Nitric oxide reductase (P) Nitrous oxide reductase (P) Ascorbate oxidase (P) Cytochrome oxidase (PM) Copper ATPase pumps (PM)... 

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... 

Pumps move ions and molecules up their electrochemical gradient. Pumps require energy, usually in the form of ATP hydrolysis. Sodium-potassium ATPase is an example of a pump. Cells maintain a higher concentration of potassium inside the cell than they do outside the cell. Sodium is maintained low inside, high outside. Sodium-potassium ATPase pumps three sodium ions from inside the cell to outside. This is the unfavorable direction—Na+ moves from low concentration to a higher one and against the membrane potential. At the same time, it also... 

The answers are 406-c, 407-g. (Hardman, pp 907—9097 926-927.) Omeprazole, which is an inhibitor of the parietal cell H+,lC,ATPase pump (proton pump), is the most effective means of decreasing gastric acidity This makes it the ideal agent to treat Zollinger-Ellis on syndrome, which results from increased gastric secretion due to gastrinomas. 

The V-ATPase pumps protons into Golgi-derived organelles 82... 

Two distinct mechanisms for controlling Ca at the plasma membrane are provided by a Ca2+-ATPase pump and a Na+/Ca2+ exchanger 380... 

The plasma membrane Ca2+-ATPase pump effects outward transport of Ca2+ against a large electrochemical gradient for Ca2+. The mechanism of the pump involves its phosphorylation by ATP and the formation of a high-energy intermediate. This basic mechanism is similar for both the plasma membrane and ER pumps however, the structures of these distinct gene products are substantially different. As discussed below, the ER pump, sometimes called a sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) pump, is inhibited potently by certain natural and synthetic toxins that do not affect the plasma membrane pump. The plasma membrane pump, but not the SERCA pump, is controlled in part by Ca2+ calmodulin, allowing for rapid activation when cytoplasmic Ca2+ rises. 

F-ATPases (including the H+- or Na+-translocating subfamilies F-type, V-type and A-type ATPase) are found in eukaryotic mitochondria and chloroplasts, in bacteria and in Archaea. As multi-subunit complexes with three to 13 dissimilar subunits, they are embedded in the membrane and involved in primary energy conversion. Although extensively studied at the molecular level, the F-ATPases will not be discussed here in detail, since their main function is not the uptake of nutrients but the synthesis of ATP ( ATP synthase ) [127-130]. For example, synthesis of ATP is mediated by bacterial F-type ATPases when protons flow through the complex down the proton electrochemical gradient. Operating in the opposite direction, the ATPases pump 3 4 H+ and/or 3Na+ out of the cell per ATP hydrolysed. 

Figure 1.3 Selective-binding sites in transport proteins for Na+, K+, Ca2+ and Cl. (a) Two Na+ binding sites in the LeuT Na+-dependent pump, (b) Four K+ binding sites in the KcsA K+ channel, (c) Two Ca2+ binding sites in the Ca2+ ATPase pump, (d) Two central Cl binding sites in a mutant C1C Cl /H+ exchanger. (From Gouax and MacKinnon, 2005. Copyright (2005) American Association for the Advancement of Science.)...

Figure 11.8). In addition, the activated enzyme phosphorylates itself, and thus remains partly active even after the Ca2+ concentration falls and calmodulin is released from the enzyme. In contrast to the CaM kinases, another important target of Ca2+-cahnodulin is the plasma membrane Ca2+-ATPase pump, whose activation drives down the Ca2+ concentration within the cell, helping to terminate the signal. 

ATP is used not only to power muscle contraction, but also to re-establish the resting state of the cell. At the end of the contraction cycle, calcium must be transported back into the sarcoplasmic reticulum, a process which is ATP driven by an active pump mechanism. Additionally, an active sodium-potassium ATPase pump is required to reset the membrane potential by extruding sodium from the sarcoplasm after each wave of depolarization. When cytoplasmic Ca2- falls, tropomyosin takes up its original position on the actin and prevents myosin binding and the muscle relaxes. Once back in the sarcoplasmic reticulum, calcium binds with a protein called calsequestrin, where it remains until the muscle is again stimulated by a neural impulse leading to calcium release into the cytosol and the cycle repeats. 

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

The regulation of intracellular neuronal Ca2+ is of high functional significance. Ca2+-dependent neurotransmitter release is reduced by the Ca2+/ATPase pump (Fossier et al. 1993). Although immediate Ca2+ currents are mediated by ionotropic glutamate receptors (i.e., NMDA) in hippocampal neurons, a sizable portion of neurons show delayed Ca2+ increases from intracellular pools (Miller et al. 1996). These delayed changes were synaptically mediated and dependent upon endosomal Ca2+/ATPase. 

Panfoli I, Musante L, Morelli A, Thellung S, Cupello A. (1997). Ca(2+)-ATPase pump forms and an endogenous inhibitor in bovine brain synaptosomes. Neurochem Res. 22(3) 297-304. 

Inorganic ions, such as sodium and potassium, move through the cell membrane by active transport. Unlike diffusion, energy is required for active transport as the chemical is moving from a lower concentration to a higher one. One example is the sodium-potassium ATPase pump, which transports sodium [Na ] ions out of the cell and potassium [K ] into the cell. 

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. 

Proton pump inhibitors (PPIs), eg, omeprazole, lansoprazole Irreversible blockade of H +, K+-ATPase pump in active parietal cells of stomach Long-lasting reduction of stimulated and nocturnal acid secretion Peptic ulcer, gastroesophageal reflux disease, erosive gastritis Half-lives much shorter than duration of action low toxicity reduction of stomach acid may reduce absorption of some drugs and increase that of others... 

This must obviously be the opposite of passive transport. Active transport does require energy, usually in the form of the consumption of ATP or GTP, because the molecules are moving against the concentration gradient from an area of lower concentration to an area of higher concentration. The most well known active transport system is the Sodium-Potassium-ATPase Pump (Na" "- K+ZATPase) which maintains an imbalance of sodium and potassium ions inside and outside the membrane, respectively. See Figure 3. 

Sodium-Potassium ATPase Pump An Active Transport System... 

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