Cytoplasmic Ca2+ levels

Intracellular Ca2+-levels are controlled by release into, and removal from, the cytoplasm (Fig. 1). Ca2+-pumps in the plasma membrane and endoplasmic reticulum (ER the Ca2+-store in a cell) keep cytoplasmic Ca2+-levels low (about 0.1 pmol/L in resting cells) and generate a 10,000-fold concentration gradient across membranes (because extracellular Ca2+ is in the millimolar range). Upon stimulation, Ca2+ enters the cytosol of the cell via Ca2+-channels (plasma membrane) or via Ca2+-channels in the ER, leading to the activation of a great variety of Ca2+-dependent processes in the cell. 

These studies all support the hypothesis that external stimuli of the elicitor cause an increase in the cytoplasmic Ca2+ level via the phosphatidylinositol cycle and/or the adenylate cyclase system. Although an authoritative picture of this process cannot yet be given, possible signal transduction mechanisms are summarized in Fig. (2). At present the data... 

De A, Churchill F, Obal F, Jr., Simasko S, Krueger JM. GHRH and IF1( increase cytoplasmic Ca2+ levels in cultured hypothalamic GABAergic neurons. Brain Res 2002 949 209-212. 

During the last ten years, it has become apparent that calcium-dependent papain-like peptidases called calpains (EC 3.4.22.17) represent an important intracellular nonlysosomal enzyme system [35][36], These enzymes show limited proteolytic activity at neutral pH and are present in virtually every eukaryotic cell type. They have been found to function in specific proteolytic events that alter intracellular metabolism and structure, rather than in general turnover of intracellular proteins. Calpains are composed of two nonidentical subunits, each of which contains functional calcium-binding sites. Two types of calpains, i.e., /i-calpain and m-calpain (formerly calpain I and calpain II, respectively), have been identified that differ in their Ca2+ requirement for activation. The activity of calpains is regulated by intracellular Ca2+ levels. At elevated cytoplasmic calcium concentrations, the precursor procal-pain associates with the inner surface of the cell membrane. This interaction seems to trigger autoproteolysis of procalpain, and active calpain is released into the cytoplasm [37]. 

Okano et al. [84] measured changes in cytoplasmic Ca2+ concentrations in platelets adhering to HEMA-STY block copolymer (HSB) surfaces by means of fluorescence microscopy combined with a high performance image processor. Comparative studies were also carried out with the HEMA-STY random (HSR) copolymer of poly HEMA and polystyrene. Their results showed that cytoplasmic free calcium levels in platelets that were in contact with the HEMA-STY... 

In muscle cells, the contraction is induced by Ca2+ release from the sarcoplasmic reticulum, as a result of membrane depolarization and activation of RyRl receptors located at the surface of the SR. The subsequent transport of cytoplasmic Ca2+ back into the lumen of the sarcoplasmic reticulum restores low resting calcium levels and allows muscle relaxation. In fast-twitch skeletal muscle fibers, Ca2+ uptake is mediated by the sarco(endo)plasmic reticulum Ca2+ ATPase SERCA1 which represents more than 99% of SERCA isoforms in these muscle fibers. 

Mechanisms that then restore the basal cytosolic [Ca2+] levels remain unclear. Besides a Ca2+-ATPase on the osteoclast dorsal surface relatively little is known of alternative or parallel methods for Ca2+ extrusion (Zaidi et al., 1993) although there is recent functional, evidence for a Na+/Ca2+ exchanger that, in analogy to the regulation of cytoplasmic [Ca2+] in cardiac muscle could be linked to the proton extrusion that is a primary determinant of the rate and extent of bone resorption (Moonga et al., 2001). 

Ganitkevich, V.Y. and Hirche, H. (1996) High cytoplasmic Ca2-f levels reached during Ca -induced Ca release in single smooth muscle cell as reported by a low affinity Ca " indicator Mag-Indo-1. Cell Calcium, 19 391-398. 

Phospholipase A Inhibition - The liberation of arachidonic acid in stimulated platelets is inhibited by cyclic-AMP. 14,24 This action of cAMP does not seem to be a direct action on platelet phospholipase A2. Cyclic-AMP decreases the levels of free cytoplasmic Ca2+ and reduces in this way the availability of Ca2+ for phospholipase A2 activity. Trifluoperazine, which is a calmodulin antagonist, also inhibits the thrombin- or platelet activating factor-induced mobilization of arachidonic acid from platelet phospholipids.20,48... 

The GABAB-receptors, the muscarinic M2- and IVU-receptors for acetylcholine, the dopamine D2-, D3-and D4-receptors, the a2-adrenoceptors for noradrenaline, the 5-HTiA F-receptors for serotonin, and the opioid p-, 8- and K-receptors couple to G proteins of the Gi/o family and thereby lower [1] the cytoplasmic level of the second messenger cyclic AMP and [2] the open probability ofN- andP/Q-type Ca2+ channels (Table 1). The muscarinic Mr, M3- and M5-receptors for acetylcholine and the ai-adrenoceptors for noradrenaline couple to G proteins of the Gq/11 family and thereby increase the cytoplasmic levels of the second messengers inositol trisphosphate and diacylglycerol (Table 1). The dopamine Dr and D5-receptors and the (3-adrenoceptors for noradrenaline, finally, couple to Gs and thereby increase the cytoplasmic level of cyclic AMP. 

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