Volume regulation

Although blood pressure control follows Ohm s law and seems to be simple, it underlies a complex circuit of interrelated systems. Hence, numerous physiologic systems that have pleiotropic effects and interact in complex fashion have been found to modulate blood pressure. Because of their number and complexity it is beyond the scope of the current account to cover all mechanisms and feedback circuits involved in blood pressure control. Rather, an overview of the clinically most relevant ones is presented. These systems include the heart, the blood vessels, the extracellular volume, the kidneys, the nervous system, a variety of humoral factors, and molecular events at the cellular level. They are intertwined to maintain adequate tissue perfusion and nutrition. Normal blood pressure control can be related to cardiac output and the total peripheral resistance. The stroke volume and the heart rate determine cardiac output. Each cycle of cardiac contraction propels a bolus of about 70 ml blood into the systemic arterial system. As one example of the interaction of these multiple systems, the stroke volume is dependent in part on intravascular volume regulated by the kidneys as well as on myocardial contractility. The latter is, in turn, a complex function involving sympathetic and parasympathetic control of heart rate intrinsic activity of the cardiac conduction system complex membrane transport and cellular events requiring influx of calcium, which lead to myocardial fibre shortening and relaxation and affects the humoral substances (e.g., catecholamines) in stimulation heart rate and myocardial fibre tension. 

In previous reviews on this matter by Gogelein [9] and myself [10] it has been pointed out that the Cl -channels of the central nervous system and of skeletal muscle are distinct from those of non-excitable cells. The latter entity is in itself obviously heterogeneous with respect to its occurrence and function. In apolar as well as in polarized cells Cl -channels may be involved in volume regulation. As a simple rule gating of K" - and Cl -channels is likely to occur whenever cell volume has to be down-regulated [11], as is the case in regulatory volume decrease of cell volume. A simple means to induce this phenomena is the exposure of cells to hypoosmolar solutions [12]. For example Cl -channels play an important role in... 

Small Cl -channels appear to play a pivotal role in cell volume regulation and in exocytosis in general. The existence of these channels has been difficult to prove, and it is only recently that they have been identified in very many cells. 

MA Valverde, M Diaz, FV Sepulveda, DR Gill, SC Hyde, CF Higgins. (1992). Volume-regulated chloride channels associated with the human multidrug-resistance P-glycoprotein. Nature 355 830-833. 

Cell-volume regulation involves control of the content of osmotically active impermeant molecules and ions 88... 

Sardini, A., Amey, J. S., Weylandt, K.-H., Nobles, M., Valverde, M. A. and Higgins, C. F. Cell volume regulation and swelling-activated chloride channels. Biochim. Biophys. Acta 1618 153- 162, 2003. 

Kirschner, L. B. (1978). External charged layer and Na+ regulation. In Osmotic and Volume Regulation. (Alfred Benzon Symposium XI Munksgaard), Academic Press, New York, pp. 310-324. 

Polar Cell Systems for Membrane Transport Studies Direct current electrical measurement in epithelia steady-state and transient analysis, 171, 607 impedance analysis in tight epithelia, 171, 628 electrical impedance analysis of leaky epithelia theory, techniques, and leak artifact problems, 171, 642 patch-clamp experiments in epithelia activation by hormones or neurotransmitters, 171, 663 ionic permeation mechanisms in epithelia biionic potentials, dilution potentials, conductances, and streaming potentials, 171, 678 use of ionophores in epithelia characterizing membrane properties, 171, 715 cultures as epithelial models porous-bottom culture dishes for studying transport and differentiation, 171, 736 volume regulation in epithelia experimental approaches, 171, 744 scanning electrode localization of transport pathways in epithelial tissues, 171, 792. 

Krane CM, Melvin JE, Nguyen HV, Richardson L, Towne JE, Doetschman T, Menon AG (2001) Salivary acinar cells from aquaporin 5-deficient mice have decreased membrane water permeability and altered cell volume regulation. J Biol Chem 276 23413-23420... 

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. 

Lemonnier, L., Prevarskaya, N., Shuba, Y., Vanden Abeele, F., Nilius, B., Mazurier, J. and Skryma, R., 2002, Ca2+ modulation of volume-regulated anion channels evidence for colocalization with store-operated channels. Faseb J 16, 222-4. 

Okada, Y. and Maeno, E., 2001, Apoptosis, cell volume regulation and volume-regulatory chloride channels. Comp Biochem Physiol A Mol Integr Physiol 130, 377-83. 

Shen, M. R., Droogmans, G., Eggermont, J., Voets, T., Ellory, J. C. and Nilius, B., 2000, Differential expression of volume-regulated anion channels during cell cycle progression of human cervical cancer cells. J Physiol 529 Pt 2, 385-94. 

Waldegger, S., Matskevitch, J., Busch, G.L. et al. Introduction to cell volume regulatory mechanisms, in Cell Volume Regulation, Lang, F. ed., Vol. 123. Basel Karger, 1998 pp. 1-7. 

Wehner, F., Olsen, H., Tinel, H. et al. Cell volume regulation osmolytes, osmolyte transport, and signal transduction. Rev. Physiol. Biochem. Pharmacol. 2003 148 1-80 (Epub 2003 Apr 4). 

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