Cell volume, regulation intracellular

Hoffmann, E.K., Simonsen, L.O., Lambert, I.H. (1993). Cell volume regulation Intracellular transmission. In Interactions of Cell Volume and Cell Function (Lang, F. Haussinger, eds.), pp. 187-248, Springer-Verlag, Heidelberg. 

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. 

Fig. 2 Schematic illustration of the possible role of K+ channels in [Ca2+]j, cell volume regulation and intracellular alkalization in tumor cells. Activation of K+ channels causes membrane hyperpolarization that in turn increases Ca2+ entry by increasing the driving force for Ca2+ and causes H+ extrusion by enhancing Na+/H+ exchanger activity leading to intracellular alkalization increased Ca2+ entry and intracellular alkalization induce Ca2+ release from Ca2+ store, leading to an increase in [Ca2+]i. Activation of K+ channels also causes H2O outflow due to hypotonic cytoplasm as a result of K+ efflux, leading to cell volume regulation...

In a dilute medium, synthesis of water results with production of ATP, whereas in a concentrated medium, synthesis of amino acid occurs. In both cases the process leads to the isosmotic regulation of intracellular fluid and therefore the maintenance of a constant cell volume.9... 

CaSR may also influence the proliferative and apoptotic status of the cells indirectly via modulation of cell volume homeostasis. Indeed, stimulation of CaSR in human epithelial cells induces upregulation of volume-regulated anion channels (VRAC) via a G protein-mediated increase in intracellular cAMP (Shimizu, et al., 2000). Proliferation and apoptosis are associated with essential volume perturbations [e.g., (Lang, et al., 2000)] and VRAC, a key component of homeostatic volume regulation, has been directly implicated in proliferation (Chen, et al., 2002, Doroshenko, et al., 2001, Shen, et al., 2000, Wang, et al., 2002) and apoptosis (Lemonnier, et al., 2004, Okada, et al., 2001, Okada, et al., 2006, Shen, et al., 2002). Consequently, extracellular Ca2+ may affect carcinogenesis via the CaSR-VRAC-cell volume links. The Ca2+ -permeable store-operated channel (SOC) is directly and functionally coupled to VRAC in an androgen-dependent LNCaP human prostate cancer epithelial cell line (Lemonnier, et al., 2002), evidence for another, CaSR-unrelated, potential mechanism for extracellular Ca2+ involvement in proliferative and apoptotic events. 

Although regulation of cell function by cell hydration has been studied most extensively in liver and renal cells, there is growing evidence that cell volume also determines cell function in other cell types. Moreover, alterations in cell hydration affect the volume of intracellular organelles, thereby modifying their function. For example, there is a close relationship between mitochondrial volume changes and mitochondrial function (see Halestrap, 1989,1993). 

Bcl-2 and Bc1-Xl can potentially translocate molecules across membranes. Bcl-2 and Bc1-Xl may interact physically or functionally with the MPT pore or with non-MPT pore proteins that control volume regulation of the matrix. In several experimental paradigms, Bcl-2 further reduces the cellular redox potential. Moreover, free radical-induced cell death is accompanied by lipid peroxidation, which is attenuated with Bcl-2 overexpression. More research is needed to determine whether intracellular redox status is a key regulator in apoptosis-signaling pathways. 

The CT channels are essential for any form of CT movement, and consequently for CT-associated processes. These proteinaceous pores in the plasma membrane or in intracellular organelles have a function for ion homeostasis, ion transport, cell volume and regulation of electrical excitability (Jentsch et al. 2002). 

Whether or not the active transport of monovalent cations is rapidly increased by serum was not known when our investigation was started. There were reports of a several-fold increase in the activity of the Na+K+ ATPase after serum feeding and this is the enzyme responsible for the action of the sodium pump , which pumps out Na+ and pumps in K+. 13,i4> However, the ATPase measurements were made 24 hours after serum addition and we were interested in rapid responses. The question of serum effects on cation transport is important because the maintenance of an asymmetric distribution of K+ and Na+ ions has a profound influence in the regulation of cell functions such as cell volume,<45) transport of non-electrolytes,membrane potential,activity of glycolytic enzymes ) and macromolecular synthesis. 7) Thus, alteration in ionic pumping activity is another potential point of control in linking surface and intracellular events. 

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