Postulated membrane pumps

The postulated proton pumps would lead either to bulk accumulation of protons in the intermembrane space and cytoplasm, with a corresponding drop in pH, or to an accumulation of protons along the membrane itself. The latter would be expected if counterions X do not pass through the membrane with the protons. The result in such a case would be the development of a membrane potential, a phenomenon already well documented for nerve membranes (Chapter 8). 

The significance of the data shown in Table 3 can be fully grasped if one realizes the fact that they represent only the tip of an iceberg of the total energy need. A by no means thorough search of the literature made in 1968 revealed that more than 20 pumps besides the Na pump have been postulated (Table 4), and more have been added.All of these postulated pumps are plasma membrane pumps. Now, as a rule, subcellullar structures like the mitochondria, contain ions and other solutes at levels different from those in the cytosol. Thus more pumps must be postulated at... 

This obvious dependence on extracellular calcium is somewhat unexpected because (1) the sustained enhancement of calcium influx rate is adequately balanced by an increase in calcium efflux rate so that (2) the calcium concentration in the bulk cytosol is maintained near the basal value. This apparent paradox may be resolved by a model [54] which postulates that during the sustained phase of cellular response the high rate of calcium cycling across the plasma membrane raises the calcium concentration in a region just below the plasma membrane, often called the submembrane domain (see Rasmussen and Barrett, Chapter 4). Because the elevated calcium level in this domain is not conducted into the bulk cytosol, it cannot activate calcium-dependent response elements in the cytosol. Rather it regulates the activity of calcium-sensitive, plasma membrane-associated enzymes such as the calcium pump and PKC, the previously described phospholipid-dependent, calcium-activated protein kinase. 

Resistance is due to the increased expression of a membrane glycoprotein "pump" which lowers the intracellular concentration of the chemotherapeutic agent. It has been postulated that a "multidrug resistance gene" is amplified in cancer cells, which is responsible for the cross-resistance. 

The next important postulate of Mitchell s theory concerns the consumers of the energy produced by primary pumps and presupposes the presence in the organella membranes of secondary proton pumps which use the transmembrane proton flow for ATP synthesis and a number of other processes. Essential to this theory is the... 

The multidrug resistance protein family (MRP) of membrane export pumps has recently been shown to be implicated in prostanoid transport. MRP4 mediates the transport of PGEj and PGE, also displaying affinity for PGEj, PGAj and TXB (Reid etal., 2003). MRP4 is widely expressed in different cells and tissues, and it has been postulated that this may be the main transport system for prostanoids (Warner and Mitchell, 2003). 

At the peritubular cell boundary (Table II, Fig. 3) the measured membrane potential (E ) of 72,0 1.4 mV and the calculated K" " equilibrium potential (Ej ) of 75.4 1,0 mV are not significantly different. Thus potassium ion is also in an electro-chemical equilibrium distribution across the peritubular cell border. In the absence of any net movement of K across the peritubular membrane we do not need to postulate the presence of an active K" " influx component as part of the peritubular Na+ pump. 

The experiment on the Na pump that established occlusion took advantage of the fact that this enzyme forms a phosphorylated intermediate. In the presence of 100 mM of Na and ATP, phosphoenzyme is formed at a constant rate. Various other cations can substitute for K in the dephosphorylation reaction, such as Rb, Cs, or NH/. These are K surrogates. If the concentration of these cations is set to give equal rates of dephosphorylation, but the enzyme turns over at a different rate, the rate-limiting step must be subsequent to dephosphorylation and before rephosphorylation. It was postulated that this step was the unbinding of the occluded cation present in the membrane domain of the dephosphorylated enzyme. 

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