CALCIUM AND CALCIUM-RELATED SIGNALLING PATHWAYS IN GLOMERULAR MESANGIAL CELLS


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Abstract

1. Calcium is an important cation for many of the physiological and pathophysiological functions of the mesangial cell. Calcium binds to many proteins in the cell. Some of these proteins seemingly serve, primarily, as intracellular buffers for calcium, whose intracellular concentration must be strictly controlled. In addition to these buffering proteins, a large number of proteins are regulated by calcium. These proteins are important for mesangial cell structural integrity, maintenance of internal ionic composition, contractility, effector responses to a variety of hormones and growth factors, and production of inflammatory mediators.2. Calcium homeostasis in mesangial cells is complex. Cells respond to vasoactive peptides and growth factors with increases in intracellular free calcium ([Ca2+]i) due to Ca2+ release from intracellular storage sites and entry across the cell plasma membrane.3. Individual mesangial cells respond to arginine vasopressin with repetitive [Ca2+]i spikes. Increasing the concentration of vasopressin up to 10 nmol/L increases the frequency of the repetitive Ca2+ spikes. The amplitude of the oscillations does not vary with the concentration of vasopressin used.4. The presence of Ca2+ oscillations whose frequency varies with ligand concentration suggests that the Ca2+ signal may encode its information through a frequency-dependent mode in addition to, or rather than, an amplitude-dependent mode. Calcium can change the conformation of proteins and can change catalytic activity of enzymes directly.5. Another important mode of regulation by calcium is demonstrated by cytosolic phospholipase A2, where calcium is important not for catalytic activity directly but for the apposition of enzyme with substrate so that the catalytic activity may be manifest.

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