ATPases, activation volumes

Toxicants that reduce ATP disrupt cell volume, ion concentrations, and cell polarity. Disruption of cell volume and ion homeostasis occurs by toxicant interaction with the plasma membrane increasing ion permeability or by attenuahng energy produchon. ATP depletion results in a decrease in Na, K -ATPase activity, resulting in cell swelling, and ultimately cell rupture [54, 55]. The tubular epithelia are polarized cells with specific transporters on the apical and basolateral domains. When a toxicant causes ATP depletion there is a dissociation of the Na, K -ATPase from the actin cytoskeleton and a redistribution from the basolateral to apical domain in the renal proximal tubule cells [56]. The loss of polarity of the cells disrupts the adhesion complexes and loss of cell-to-cell contact that facilitates further renal damage. 

Twitch duration is largely a function of how extensive the SR is. In FT fibers, SR accounts for roughly 15% of the cell volume, whereas it is only about 3-5% in ST fibers. The total RyR Ca + conductance and the total SR Ca " "-ATPase activity reflects this, so that the rates of Ca + release in the E-C coupling phase, the peak sarcoplasmic [Ca +] achieved in a twitch, and the reuptake rate of Ca " " are all 2-A times greater in FT fibers than in ST fibers. These differences result in the shorter time to peak tension, higher twitch tension, and shorter half-relaxation time seen in FT fibers compared to ST. 

Based on these findings, one can conclude that arachidonic acid metabolism in mTALH via the cytochrome P450-dependent pathway is stimulated by either AVP or SCT via an adenylate cyclase-coupled receptor. Moreover, one or more of the arachidonic acid metabolites formed modulate Na -K -ATPase activity and thereby contribute to the regulation of extracellular fluid volume. A factor which diminishes the activity of Na -K -ATPase in the mTALH has been postulated to account for exaggerated natriuresis in response to volume expansion in hypertension ... 

The studies were performed on CFq-CFi complex is isolated according to (4) and on soluble protein CFi obtained according to (5) from bean chloroplasts. After the thermal activation (6) the latter had the ATPase activity about 30 pmol ATP/mg protein per minute (7). The pH shift was obtained by mixing equal volumes of solutions A and B. Solution A A mM NaH2P04, pH 4.5 4 x 10"° protein, 1 mM CaCl2 (for CFi) or 1 mM MgCl2 (for CFq-CFi) and 10"°M ADP. Solution B ... 

Additional cellular events linked to the activity of blood pressure regulating substances involve membrane sodium transport mechanisms Na+/K.+ ATPase Na+fLi countertransport Na+ -H exchange Na+-Ca2+ exchange Na+-K+ 2C1 transport passive Na+ transport potassium channels cell volume and intracellular pH changes and calcium channels. 

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. 

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