Cellular calcium regulation

Cellular calcium regulation. Depicted are several sites that control calcium entry, efflux, and sequestration. 1. Na+, Ca++ exchange. 2. Receptor-operated channels. 3. Voltagegated channels. 4. Leak pathways. 5, 6. Entry and efflux in sarcoplasmic reticulum. 7. Plasma membrane pump. 

The stepwise reduction of oxygen produces hydrogen peroxide, and finally, a hydroxyl radical, which is a strong oxidant implicated in cellular oxidative stress. This oxidative stress causes glutathione depletion, a disruption of the cellular calcium regulation and modifications of cellular proteins, thus... 

Cellular Calcium Regulation Calciiun plays critical roles in cellular communication and regulation. The normally very low resting free ionized concentration of Ca is maintained by a variety of ion channels, pumps, and intracellular storage processes. The elevation of intracellular Ca levels during cell stimulation serves to couple information with cellular response -stimulus-response coupling. The control of Ca " homeostasis represents, therefore, a potentially powerful control of cellular excitability and response [ 5 ]. 

Alio S.N., Lincoln T.M., Wilson G.L., Green F.J. Watanabe A.M., Schaffer S.W. Noninsulin-dependent diabetes-induced defects in cardiac cellular calcium regulation. Am. J. Physiol. Cell. Physiol. 260 (1991) C1165-C1171. 

The sarcolemmal Na/K pump plays an imp>ortant, although indirect role in the regulation of cellular calcium homeostasis. The transmembrane Na gradient is maintained by the activity of the Na/K pump and the thermodynamic energy of this gradient in turn drives the Na/Ca exchange mechanism (Sheu and Fozzard, 1982 Barry and Bridge, 1993). Thus, the intracellular Ca concentration is closely related to intracellular Na and the activity of the Na/K pump (Bers and Ellis, 1982). 

Carafoli, E., Santella, L., Branca, D., and Brini, M., 2001, Generation, control, and processing of cellular calcium signals, Crit. Rev. Biochem. Mol. Biol. 36, pp. 107-260 Chalmers, S. and Nicholls, D. G., 2003, The Relationship between Free and Total Calcium Concentrations in the Matrix of Liver and Brain Mitochondria, J. Biol. Chem. 278, p. 19062 Colell, A., Garcia-Ruiz, C., Mari, M., and Fernandez-Checa, J. C., 2004, Mitochondrial permeability transition induced by reactive oxygen species is independent of cholesterol-regulated membrane fluidity, FEBS Lett 560, pp. 63-68... 

In this chapter, we will describe calcium transport and calcium regulation from the standpoint of bulk mineral transport, and then from the standpoint of cellular regulation. We will use inborn errors of metabolism where possible to illustrate the major calcium-related activities of the cells. After the framework of functional calcium transport is established, we will discuss calcium-dependent cellular regulatory functions. 

Diacylglycerol was mentioned as an activator of protein kinase C. In addition to diacylglycerol, protein kinase C is also activated by increased cellular calcium levels. Protein kinase C catalyzes, for example, the phosphorylation of G protein components the j8 subunit of the fiy complex and the a-GDP complex. Such phosphorylation apparently prevents the reassociation of the a-GDP with the fiy complex to give the G -GDP protein. It is thus clear that phosphorylation via protein kinase C participates in the regulation of G protein function. 

Potassium channels represent a very large and diverse collection of membrane proteins which participate in important cellular functions regulating neuronal and cardial electrical patterns, release of neurotransmitters, muscle contractility, hormone secretion, secretion of fluids, and modulation of signal transduction pathways. Main categories of potassium channels are gated by voltage or an increase of intracellular calcium concentration (Escande and Henry 1993 Kaczorowski and Garcia 1999 Alexander et al. 2001). 

Calcineurin (protein phosphatase 2B) is a Ser/Thr phosphatase that is controlled by cellular calcium and regulates a large number of biological responses including lymphocyte activation, neuronal and muscle development, and the development of vertebrate heart valves. 

Friedman PA, Gesek FA. 1995. Cellular calcium transport in renal epithelia Measurement, mechanisms and regulation. Physiol Rev 75 429-471. 

The activation of protein kinase C and subsequent induction of cell proliferation by cytotoxic chemicals has been suggested by Roghani et al. (64). The inappropriate activation of this enzyme by a chemical-receptor complex is believed to play a role in the promotion process. The activation of protein kinase C may subsequently result in the activation of a number of cytoplasmic proteins through inductional phosphorylation and set off a chain of events which includes enhanced cell proliferation in the absence of regenerative cell replication. The distinction between cytotoxicity and promotion may not always be clear. As recently discussed by Trump and Berezesky (65), chemically-induced alterations in the cellular dynamics of calcium regulation may result in a wide range of changes, many of which are similar to those caused by protein kinase C... 

An important contribution to systemic Ca homeostasis comes from the extracellular calcium-sensing receptor (CaR) (Mithal and Brown 2003). The CaR is a G protein-coupled plasma membrane receptor, by which minute variations in [Ca +] are transduced into changes in cellular functions, including proliferative activity. The CaR is expressed not only in the parathyroid gland (Brown et al. 1993), but importantly also on cells of the main calcium-regulating organs, such as bone (Yamaguchi et al. 

Somlyo AP (1984) Cellular site of calcium regulation. Nature 308 516-517 Somlyo AP (1993) Myosin isoforms in smooth muscle how may they affect function and structure J Mus Res Cell Motil 14 557-563. 

---