Calcium cellular functions

As stated above, calcium is an extremely important cellular ion for several cellular functions. The concentration of calcium in human extracellular fluid is about 2.5 mM, while the intracellular concentration is only 100-200 nM depending on the cell type. Thus, there is 10 000-20 000 fold concentration difference between the cell interior and exterior that has to be maintained by cellular pumping mechanisms. This requires a large amount of energy. " ... 

More recent analysis of tissue specific gene deletions showed that the Cav1.2 channel is involved in a wide variety of function including hippocampal learning, insulin secretion, intestine and bladder motility. Further analysis will be required to unravel the functional significance of voltage-dependent calcium channels for specific cellular functions. 

There are at least five different types of voltage-dependent Ca2+ channel molecules, differing in their gating kinetics, modes of Ca2+-inactivation and Ca2+-iregulation, and sensitivity to specific marine toxins [13] (see Ch. 6). The distinctions between the types of channel are of considerable interest because the different subtypes are believed to subserve different cellular functions. For example, the control of neurotransmitter release in peripheral sympathetic neurons appears to be under the predominant control of N-type calcium channels. 

Sodium, potassium, calcium, magnesium, phosphorus, chloride, and acetate are necessary components of PN for maintenance of numerous cellular functions. 

Calcium and phosphate, the major mineral constituents of bone, are also two of the most important minerals for general cellular function. Accordingly, the body has evolved a complex set of mechanisms by which calcium and phosphate homeostasis are carefully maintained (Figure 42-1). Approximately 98% of the 1-2 kg of calcium and 85% of the 1 kg of phosphorus in the human adult are found in bone, the principal reservoir for these minerals. These functions are dynamic, with constant remodeling of bone and ready exchange of bone mineral with that in the extracellular fluid. Bone also serves as the principal structural support for the body and provides the space for hematopoiesis. Thus, abnormalities in bone mineral homeostasis can lead not only to a wide variety of cellular dysfunctions (eg, tetany, coma, muscle weakness) but also to disturbances in structural support of the body (eg, osteoporosis with fractures) and loss of hematopoietic capacity (eg, infantile osteopetrosis). 

Even by chelating trace elements indispensable to the cellular functioning (as the calcium or the magnesium)... 

The second messenger molecules Ca2+ and cyclic AMP (cAMP) provide major routes for controlling cellular functions. In many instances, calcium (Ca2+) achieves its intracellular effects by binding to the receptor protein calmodulin. Calmodulin has the ability to associate with and modulate different proteins in a Ca2+-dependent and reversible manner. Calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE, EC 3.1.4.17) is one of the key enzymes involved in the complex interactions that occur between the cyclic-nucleotide and Ca2+ second messenger systems (see Figure 13.2). CaMPDE exists in different isozymic forms, which exhibit distinct molecular and catalytic properties. The differential expression and regulation of individual phosphodiesterase (PDE) isoenzymes in different tissues relates to their function in the body. 

A schematic representation of the cellular mechanisms through which agonists, such as dopamine, stimulate PTH release and calcium inhibits hormonal secretion is shown in Figure 11. In this schema, cAMP is a stimulatory second messenger while cytosolic calcium serves to inhibit hormone release by acting at several loci within the cell. The detailed molecular mechanisms through which cAMP and cellular calcium modulate cellular function remain to be determined. 

The role of internal hydration as a signal for cellular function may be recognized by analogy to metabolic regulation by [Ca2+] or pH . Cells possess efficient mechanisms that keep the intracellular calcium and proton concentrations within narrow limits, otherwise cells would not survive. These homeostatic mechanisms can also be used to produce small physiological changes in cell hydration, which, in turn, regulate cell function. 

The cytoskeletal network is responsible for the mechanical properties of the cell that modulate functions such as cell shape, locomotion, cytokinesis, and translocation of organelles. Experimental evidence suggests that the cytoskeleton also provides connections between cellular structures and presents a large surface area for interactions of various proteins and signaling molecules. Modulation of the cytoskeletal network may influence cell signaling, ion channels and intracellular calcium levels. Cytoskeleton is thus essential for regulation of cellular functions, cell integrity, and viability. 

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). 

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