Cytoplasmic Calcium Levels Research Articles

Complementary vascular-protective actions of magnesium and taurine: A rationale for magnesium taurate

By a variety of mechanisms, magnesium functions both intracellularly and extracellularly to minimize the cytoplasmic free calcium level, [Ca 2+] i. This may be the chief reason why correction of magnesium deficiency, or induction of hypermagnesemia by parenteral infusion, exerts anti hypertensive, anti-atherosclerotic, anti-arrhythmic and antithrombotic effects. Although the amino acid taurine can increase systolic calcium transients in cardiac cells (and thus has positive inotropic activity), it has other actions which tend to reduce [Ca 2+] i. Indeed, in animal or clinical studies, taurine lowers elevated blood pressure, retards cholesterol-induced atherogenesis, prevents arrhythmias and stabilizes platelets — effects parallel to those of magnesium. The complex magnesium taurate may thus have considerable potential as a vascular-protective nutritional supplement, and might also be administered parenterally, as an alternative to magnesium sulfate, in the treatment of acute myocardial infarction as well as of pre-eclampsia. The effects of magnesium taurate in diabetes deserve particular attention, since both magnesium and taurine may improve insulin sensitivity, and also may lessen risk for the micro- and macrovascular complications of diabetes.

Cytoplasmic calcium level and membrane fluidity of platelets contacting poly(acrylamide-co-methacrylic acid) particles with different surface properties.

Changes in cytoplasmic free calcium levels and membrane fluidity of platelets in contact with poly(acrylamide-co-methacrylic acid) (PAAmMAc) particles were examined to analyze the mechanistic aspect of regulating platelet function. Our previous studies demonstrated interesting features of PAAmMAc particles during interaction with platelets: (1) PAAmMAc particles induce no calcium increase but enhance membrane fluidity of platelets: (2) thrombin induces no calcium increase in platelets when the platelets were mixed previously with PAAmMAc particles; and (3) PAAmMAc particles induce a calcium increase in platelets when they were treated previously with sodium azide (NaN3). These results suggest the possibility that PAAmMAc surfaces may regulate the calcium level by influencing platelet metabolism. In this study, non-cross-linked PAAmMAc solution with the same chemical composition as the particles showed a suppressive effect on thrombin-induced calcium increase, but, no influence on membrane fluidity. This result indicates that aggregated macromolecular surface assemblies of PAAmMAc may dominate the increase in membrane fluidity of platelets although the calcium change is induced by discrete molecular level interaction between the PAAmMAc and platelet membranes. It was also revealed that the suppression of thrombin-induced calcium increase and the membrane fluidity increase in platelets by PAAmMAc particles were reduced by albumin-treatment of the particles. This result suggests that such phenomena may be due to a decrease in any physicochemical interaction of PAAmMAc surfaces with albumin, rather than platelet metabolic change. PAAmMAc particle surfaces with higher carboxyl groups exhibited a more suppressive effect on thrombin-induced calcium increase, whereas those with lower carboxyl groups derived a higher calcium increase when the platelets were treated previously with NaN3. These results suggest the importance of electrostatic and any other physicochemical interaction of PAAmMAc chains on regulating cytoplasmic calcium levels.

Divergent Phosphotyrosine Signaling via FcγRIIIA on Human NK Cells

Previous studies have indicated that interaction of FcγRIIIA on natural killer (NK) cells with various immunoglobulin ligands or monoclonal antibodies (mAbs) can have either stimulatory or inhibitory effects on cytotoxic activity, but the basis for such divergent functional effects has been unclear. We report here that stimulation of NK cells via FcγRIIIA by monoclonal anti-human CD16 (3G8), monomeric IgG (mIgG), or dimeric IgG (dIgG), used either alone or cross-linked by secondary Ab (goat anti-mouse IgG or goat anti-human IgG), resulted in different phosphotyrosine protein patterns. These results suggest that distinct substrates are involved in signaling pathways activated via various agonists of the same triggering surface molecule. Three protein tyrosine kinases, i.e., LCK, LYN, and SYK, were activated by occupancy of the FcγRIIIA, and only LCK activity showed a divergence in effects induced by the various ligands, with strong autophosphorylation induced by mIgG upon cross-linking. We observed no ligand-induced activation of p59fyn, p60c-src, or p62c-yes, src-related protein tyrosine kinases which are expressed in NK cells. Activity of phosphatidylinositol 3-kinase (PI 3-kinase) induced by receptor-specific antibodies or IgG ligands had different kinetics while the level of cytoplasmic free calcium was greatest upon 3G8-induced stimulation. Although the changes in kinase activities associated with FcγRIIIA-mediated regulation of NK cells are complex, it appears that the patterns induced varied with the nature of the ligand and the direction of the regulation of NK activity.

The Cytoplasmic Streaming Response of Tomato Root Hairs to Auxin; the Role of Calcium

The effects of IAA on the cytoplasmic streaming response of tomato root hairs were observed at different external calcium concentrations. The sensitivity of tomato root hairs to IAA was increased by increasing the calcium content of the bathing medium; lower concentrations of IAA were needed to stimulate cytoplasmic streaming at high [Ca2+]ext. The transplasma membrane electrical potential difference was rapidly depolarised by IAA across a wide range of auxin and calcium concentrations; subsequent hyperpolarisation was only seen in the presence of high [Ca2+]ext. Measurements of cytoplasmic calcium levels, using the dye fluo-3, revealed the dynamic nature of the cytoplasm. As in earlier experiments, in which indo-1 and fura-2 were used, IAA appeared to have only small effects on [Ca2+]cyt. Clear, auxin-induced changes in [Ca2+]cyt were recorded only under non-physiological conditions.

Intracellular calcium reaches different levels of elevation in hyperactivated and acrosome‐reacted hamster sperm

Calcium plays a role in sperm motility hyperactivation and the acrosome reaction, but the relationship between cytoplasmic calcium (Ca2+in) levels in the two states was heretofore unknown. The Ca2+ indicator indo-1 was used to detect Ca2+in in moving hamster sperm in two sets of experiments. In the first experiment, activated, hyperactivated, and zona pellucida-induced acrosome-reacted/hyperactivated sperm were analyzed at the time of peak of activity for each state. In the second experiment, sperm in all states were analyzed at one time point. In both sets, mean Ca2+in in the acrosomal region, postacrosomal region, and flagellar midpiece was greater in hyperactivated sperm than in activated sperm, and in acrosome-reacted/hyperactivated sperm than in unreacted/hyperactivated sperm (P < 0.001). Ca2+in had increased to a greater extent in the midpiece than in the head in hyperactivated sperm, while the reverse was true for acrosome-reacted sperm. Oscillations at the frequency of the flagellar beat cycle were detected chiefly in the proximal flagellar midpiece of acrosome-reacted sperm, as they had been previously reported to occur in activated and hyperactivated sperm. Thus, Ca2+in may be maintained at two different elevated levels in sperm, and continues to oscillate after the acrosome reaction.

Chronic overcrowding decreases cytoplasmic free calcium levels in T lymphocytes of aged CBA/CA mice.

Intracellular calcium concentration is a sensitive marker of the homeostasis of living cells, and its increase is an essential step of T lymphocyte activation. Changes in the environment provoke an adaptive stress-response of the organism. In our present work we have investigated the effect of chronic overcrowding on resting and lectin-stimulated cytoplasmic free calcium concentration of splenic T lymphocytes from young and aged CBA/CA mice (50 animals total). The animals were kept under 'normal' (68 cm2/animal) or 'overcrowded' (22 cm2/animal) conditions for 3 months. Young animals showed no change in resting and stimulated calcium after overcrowding. T cells from aged mice, however, displayed significantly smaller levels of both resting and lectin-stimulated intracellular calcium concentration (p < 0.01 each), as compared to those of the non-stressed, aged animals. This inadequate adaptation in the calcium metabolism of T lymphocytes may significantly contribute to the diminished immune response of the aged in stress.

Angiotensin II mediates a sustained rise in nuclear and cytoplasmic calcium via multiple receptor subtypes.

Alterations in nuclear calcium levels in response to angiotensin II (ANG II) may play an important role in the trophic actions of ANG II. This study utilized confocal microscopy and nuclear staining to test the hypothesis that both nuclear and cytoplasmic calcium levels are altered in response to ANG II stimulation of freshly dissociated aortic smooth muscle cells. Cells were loaded with the calcium indicator fluo 3 acetoxymethyl ester, and the calcium response to ANG II stimulation was analyzed over time with a laser-scanning confocal microscope. Additionally, the ratiometric calcium indicator fura 2 acetoxymethyl ester and conventional fluorescence microscopy were used to verify these observations. Results show that basal nuclear calcium exceeds cytoplasmic calcium in these cells. Stimulation by ANG II induces a sustained rise (separate from the rapid transient) in both nuclear and cytoplasmic calcium in excess of 20 min in duration. This rise was blockable by either the AT1 receptor antagonist DuP-753 or by the AT2 antagonist PD-123319. Thus ANG II stimulates a sustained rise in nuclear calcium by a mechanism that necessitates activation of both AT1 and AT2 receptors.

Characteristics of nucleotide receptors that cause elevation of cytoplasmic calcium in immortalized rat brain endothelial cells (RBE4) and in primary cultures.

1. A dual-wavelength microfluorimetric method using Fura-2 as calcium indicator was applied to cells from an immortalized cell line of rat brain microvascular endothelial cells (RBE4), and to primary cultured rat brain endothelial cells. 2. In RBE4 cells, a brief (20 s) pulse of extracellular ATP (100 microM) induced a transient increase in the cytoplasmic calcium level ([Ca2+]i). Control responses to 100 microM ATP consisted of a ratio increase of 0.64 +/- 0.03 (mean +/- s.e., n = 51). Responses were seen at a concentration of 2.5 microM and were maximal at 100-1000 microM. When extracellular calcium was chelated with EGTA, the transient increase in [Ca2+]i was not affected. The results are consistent with Ca2+ mobilization from intracellular stores. 3. The purinoceptor involved belongs to the P2 subtype, since the agonist potency order among the adenine nucleotides was ATP > ADP > AMP. Moreover, the increase in [Ca2+]i evoked by ATP was partially inhibited by the P2 antagonist, suramin but was not affected by 8-phenyltheophylline, a P1-purinoceptor antagonist. The strong desensitization observed with repeated applications of ATP is also typical of a P2 receptor. 4. 2-Methylthio-ATP (2meS-ATP 100 microM), a P2Y agonist, elevated [Ca2+]i in only 17% of the cells tested; however, 2meS-ATP was found to antagonize the effect of ATP in all cells tested. The increase in [Ca2+]i evoked by ATP was inhibited by 500 s application of the P2Y purinoceptor antagonist, Reactive Blue 2 at 10 microM, while 60 s application of 100 microM was ineffective. 5. The uracil nucleotide, UTP (100 microM) was as effective as ATP in increasing [Ca2+]i. The effects of ATP and UTP were not additive. Cells desensitized to the action of ATP (or UTP) were unable to respond to UTP (or ATP).6. alpha,beta Methylene-ATP (alpha,beta meATP 100 microM), a P2x, agonist, elevated [Ca2+], in only 40% of the cells tested. In these cells it was less effective than ATP in increasing [Ca2+]i.7. Cells desensitized to the action of ADP responded, to a smaller extent, to ATP. In contrast, cells desensitized to the action of ATP were unable to respond to ADP.8. On primary cultures of brain endothelial cells the increase in [Ca2+]i in response to extracellular ATP(100 microM) and UTP (100 microM) was of an equivalent amplitude, and similar to the response in RBE4 cells.The pattern of desensitization was also similar to that in RBE4 cells.9 This comparative study indicates that in well-characterized brain microvascular endothelial cells that retain brain endothelial characteristics, the major class of nucleotide receptor is of the P2mu type. The implications for physiology are discussed.

Calcium pyrophosphate crystal deposition disease and other crystal deposition diseases

"Tumoral" calcium pyrophosphate dihydrate (CPPD) crystal deposition in the ligamentum flavum is rare and can lead to compression myeloradiculopathy in the cervical spine and to spinal canal stenosis in the lumbar spine. CPPD crystal deposition disease is rarely associated with Bartter's syndrome and hypomagnesemia. Intramuscular corticotropin has proved effective in the treatment of acute episodes of pyrophosphate arthritis in patients with multiple medical illnesses in whom nonsteroidal anti-inflammatory drugs are contraindicated. IgG binding to CPPD crystals enhances neutrophil activation (by increasing intracellular cytoplasmic calcium levels) and seems to play a greater role in pyrophosphate than in urate crystal-induced inflammation. Transforming growth factor-beta 1 stimulates intracellular pyrophosphate generation by articular chondrocytes. The effect is inhibited by probenecid, an anion transport blocker, through interfering with the active transport of intracellular pyrophosphate to cartilage matrix where crystals form. Calcific tendinitis associated with underlying cortical bone erosions is an uncommon manifestation of apatite crystal deposition disease. Closed-needle tidal irrigation proved beneficial in two patients with Milwaukee shoulder syndrome. Two patients with nodular subcutaneous cholesterol crystal deposition are described.

Elevated striatal Fos immunoreactivity following 6-hydroxydopamine lesioning of the rat is mediated by excitatory amino acid transmission

Pharmacological depletion of dopaminergic neurotransmission can result in an elevation in striatal Fos levels. This elevation may occur as a direct result of decreased dopaminergic neurotransmission or indirectly via elevated corticostriatal glutamatergic neurotransmission which occurs secondary to dopamine depletion. To test the hypothesis that elevated N-methyl- d-aspartic acid (NMDA)-mediated corticostriatal transmission may underlie the increase in striatal Fos levels upon dopamine depletion, rats were unilaterally 6-hydroxydopamine lesioned under anaesthesia induced by either barbiturate or the NMDA antagonist, ketamine. Following surgery the animals remained under light anaesthesia for 6 h prior to sacrifice and quantification of striatal Fos immunoreactivity. The results demonstrate that dopamine depletion following 6-hydroxydopamine lesioning can result in elevated striatal Fos levels which can be attenuated by contiguous treatment with an NMDA antagonist. This suggests that the increase in striatal Fos levels observed following dopamine depletion may occur as a result of elevated cytoplasmic calcium levels in the striatal cells.

Aluminum, calcium, and iron in the spinal cord of patients with sporadic amyotrophic lateral sclerosis using laser microprobe mass spectroscopy: a preliminary study

We measured aluminum (Al), calcium (Ca), and iron (Fe) levels in neuronal cytoplasm and nucleus, capillaries, and neuropil in samples of ventral cervical spinal cord from 5 patients with sporadic amyotrophic lateral sclerosis (ALS) and 5 age-matched controls using laser microprobe mass spectrometry (LMMS). The concentration of Al was not altered in any area in the ALS samples. In contrast, Fe and Ca were increased 1.5-2-fold in the nucleus and cytoplasm of ALS neurons but not in capillaries and neuropil. These findings do not support the hypothesis that Al is enriched in spinal cord of sporadic ALS as has been reported for Guamanian ALS/Parkinson's dementia. The elevations of Fe in spinal neurons are consistent with reports of increased Fe in bulk samples of ALS spinal cord. The presence of increased Fe within spinal neurons may be significant in the pathogenesis of motor neuron degeneration by catalyzing the generation of reactive oxygen species within specific cells.

Diverging signal transduction pathways activated by interleukin-8 and related chemokines in human neutrophils: interleukin-8, but not NAP-2 or GRO alpha, stimulates phospholipase D activity

Interleukin-8 (IL-8) and the structurally related cytokines neutrophil- activating peptide-2 (NAP-2) and GRO alpha are powerful chemotactic agents for human neutrophils. Although these three chemokines act by binding to overlapping but not identical receptor subsets, the data available to date have stressed the similarities in their mechanisms of action. The present studies were undertaken to further our understanding of the signal transduction mechanisms associated with these neutrophil agonists. IL-8, NAP-2, and GRO alpha stimulated similar increases in the level of cytoplasmic free calcium. They were also shown to stimulate qualitatively similar increases in the levels of protein tyrosine phosphorylation. In contrast, only IL-8 enhanced the formation of phosphatidylethanol (PEt), the product catalyzed by phospholipase D (PLD) in the presence of ethanol. The formation of PEt stimulated by IL-8 was inhibited by pertussis toxin and the tyrosine kinase inhibitors erbstatin and herbimycin A. The ability of IL-8 to stimulate the activity of PLD was additively enhanced, or primed, by cytochalasin B and by tumor necrosis factor alpha. Although all three chemokines increased the level of free cytoplasmic calcium to the same extent, IL-8 was significantly more potent than either NAP-2 or GRO alpha with respect to its ability to enhance CD11b expression and to stimulate chemotactic and oxidative responses. The differences between IL-8, NAP-2, and GRO alpha in their ability to stimulate PLD is likely to be related to their respective binding affinities for the two IL-8 receptors (IL-8R-A and IL-8R-B). These results suggest that the signalling pathways activated by IL-8R-A and IL-8R-B diverge at a step preceding the activation of PLD.

Diverging Signal Transduction Pathways Activated by Interleukin-8 and Related Chemokines in Human Neutrophils: Interleukin-8, But Not NAP-2 or GROα, Stimulates Phospholipase D Activity

Interleukin-8 (IL-8) and the structurally related cytokines neutrophil-activating peptide-2 (NAP-2) and GRO alpha are powerful chemotactic agents for human neutrophils. Although these three chemokines act by binding to overlapping but not identical receptor subsets, the data available to date have stressed the similarities in their mechanisms of action. The present studies were undertaken to further our understanding of the signal transduction mechanisms associated with these neutrophil agonists. IL-8, NAP-2, and GRO alpha stimulated similar increases in the level of cytoplasmic free calcium. They were also shown to stimulate qualitatively similar increases in the levels of protein tyrosine phosphorylation. In contrast, only IL-8 enhanced the formation of phosphatidylethanol (PEt), the product catalyzed by phospholipase D (PLD) in the presence of ethanol. The formation of PEt stimulated by IL-8 was inhibited by pertussis toxin and the tyrosine kinase inhibitors erbstatin and herbimycin A. The ability of IL-8 to stimulate the activity of PLD was additively enhanced, or primed, by cytochalasin B and by tumor necrosis factor alpha. Although all three chemokines increased the level of free cytoplasmic calcium to the same extent, IL-8 was significantly more potent than either NAP-2 or GRO alpha with respect to its ability to enhance CD11b expression and to stimulate chemotactic and oxidative responses. The differences between IL-8, NAP-2, and GRO alpha in their ability to stimulate PLD is likely to be related to their respective binding affinities for the two IL-8 receptors (IL-8R-A and IL-8R-B). These results suggest that the signalling pathways activated by IL-8R-A and IL-8R-B diverge at a step preceding the activation of PLD.

The pathophysiology of cocaine cardiotoxicity

Cocaine use is accompanied by a high risk of serious adverse effects involving the cardiovascular system. The basic cellular mechanisms of cocaine consist in [1] a potentiation of catecholamine effects by inhibition of the presynaptic uptake carrier [2] local anesthetic effects by the block of sodium-channels. Acute ischemic events can be induced by cocaine through coronary spasms in a situation of physiologic stress already accompanied by an enhanced myocardial oxygen demand. Procoagulant properties of cocaine may, moreover, favor coronary thrombosis formation and the development of myocardial infarction. Ischemia, reperfusion and the direct action of catecholamines on cardiocytes are accompanied by enhanced cytoplasmic calcium levels, inducing delayed after-potentials, repetitive action-potential generation and premature ventricular beats. Conduction velocity impairments caused by the local anesthetic effects of cocaine and inhomogeneous repolarization phenomena related to potassium channel inhibition may form a substrate for re-entrant circuits inducing ventricular fibrillation. Cocaine abuse may also cause degenerative and inflammatory alterations of the myocardium. Besides secondary ischemic changes, hypersensitivity-myocarditis and toxic cardiomyopathies that may be due to the cardiotoxic effects of catecholamines have been described in cocaine abusers. Moreover, persons using cocaine intravenously seem to be particularly endangered by bacterial endocarditis compared to the users of other intravenous drugs, for still unknown reasons.

FK 506 and cyclosporin each block antigen-induced T cell receptor signalling that is dependent on CD 4 co-receptor and operates in the absence of detectable cytoplasmic calcium fluxes

The T cell hybridoma "171", which lacks CD4 but expresses T cell receptor (TCR) for hen egg white lysozyme, requires introduction of wild-type CD4 for antigen-mediated induction and secretion of interleukin-2 (IL-2). Mutant CD4, which fails to associate with the tyrosine kinase p56lck does not support IL-2 secretion, suggesting that a role of CD4 is to bring cytoplasmic p56lck into alignment for signal transduction to the IL-2 promotor. Using 171, 171-CD4 (wild-type) and 171-CD4 (mutant), we found that IL-2 secretion was inhibited by FK 506 and cyclosporin but not by rapamycin. However, this inhibition was not associated with calcium fluxes since no change in cytoplasmic free calcium levels ([Ca]i; resting level 80 nM) was detectable during antigen stimulation of the 171 or 171-CD4 cells. Thus, although FK 506 and cyclosporin inhibited calcium-dependent signalling to the IL-2 promoter via inhibition of the protein phosphatase calcineurin, it is possible that IL-2 induction via TCR/CD4 requires an FK 506 (and cyclosporin) sensitive step which is independent of cytoplasmic calcium changes.

Contractile failure in early myocardial ischemia: Models and mechanisms

In early myocardial ischemia we find a number of salient electrical and ionic alterations. This article reviews action potential shortening, K accumulation, and contractile failure. Enhanced K efflux during early myocardial ischemia has been attributed to a number of mechanisms, including: the inhibition of active K uptake, osmotic changes, efflux of K ions linked to anion extrusion, cation exchange, altered cellular energy levels, in particular, the opening of ATP-dependent K channels, the involvement of other ion channels, a H/K-ion exchanger, and a catecholamine-dependent pathway. The different mechanisms are discussed. Action potential shortening was described as a salient characteristic of myocardial ischemia in 1954 by Trautwein and Dudel, and was attributed to enhanced outward current. Recently it has been shown by several authors that ATP-dependent potassium channels play a key role in this context. Contractile failure in early myocardial ischemia has been explained by shortening of the action potential duration, reduced cytoplasmic free calcium levels, intracellular acidification, and a rise in inorganic phosphate and Mg. In summary, it is concluded that ATP-dependent K channels may be involved in each of these three phenomena.

FK506 and Cyclosporin A Each Inhibit Antigen-Specific Signaling in the T Cell Line 171 in the Absence of a Calcium Signal

Antigen-specific signal transduction leading to IL2 induction and secretion in the T cell line 171 is augmented by association of p56 lck with CD4. Although no change in cytoplasmic calcium level ([Ca 2+]i) was detectable during antigen-specific signal transduction of the 171-CD4 + cells, IL2 induction was inhibited by FK506 and CsA. Since these drugs are thought to act selectively by inhibiting calcineurin, a calcium-calmodulin-dependent protein phosphatase associated with activation of the IL2 promoter, we considered the possibility that calcineurin is constitutively active in 171 cells. However, we found no evidence for this because PMA failed to supplement any putatively active calcineurin to induce IL2 secretion. We suggest that IL2 secretion induced by antigen presentation to TCR/CD4/p56 kk requires an FK506 and cyclosporin A-sensitive step which may be independent of calcium signaling. Rapamycin did not inhibit IL2 secretion induced by TCR/CD4/p56 lck, emphasizing the specific action of FK506 and cyclosporin A.

Schwann Cells Exhibit P2Y Purinergic Receptors that Regulate Intracellular Calcium and Are Up‐Regulated by Cyclic AMP Analogues

Schwann cells establish close contact with axons during development, and this is maintained throughout life. Signaling by neurotransmitters may play an important role in Schwann cell-axon interaction. Schwann cells were examined for the presence of neuroligland receptors that are linked to increases in levels of cytoplasmic calcium. Schwann cell cultures were prepared from neonatal rat sciatic nerve and, after 0.25, 1, 4, 7, and 14 days in vitro (DIV), loaded with the calcium indicator dye fura 2-AM. The influence of neuroligands on the cytosolic free calcium concentration ([Ca2+]i) was then examined at each time point using a video-based imaging system. Approximately 80-95% of all freshly isolated Schwann cells responded to 10 microM ATP with a three-fold rise in [Ca2+]i. Bradykinin, glutamate, and histamine had no or only partial and inconsistent responses. The ATP-induced calcium response disappeared within 4 DIV. Culturing cells in the presence of cyclic AMP (cAMP) analogues (which induce proliferation and differentiation in vitro) restored the ability of Schwann cells to respond to ATP with increased [Ca2+]i. In the presence of cAMP analogues the extent of recovery of ATP responsiveness was dependent on serum concentration. Fifty to ninety percent of cells regained calcium responsiveness to ATP when grown in medium containing cAMP analogues and 1% serum. These cells also exhibited immunoreactivity to P0 antibody, characteristic of the myelinating lineage. In contrast, only 15-30% of the Schwann cells regained calcium responsiveness when grown in medium containing cAMP analogues and 10% serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium regulates processing of the Alzheimer amyloid protein precursor in a protein kinase C-independent manner.

Various first messengers linked to phospholipase C, including acetylcholine and interleukin 1, regulate the production both of the secreted form of the amyloid protein precursor (APP) and of amyloid beta-protein. We have now identified intracellular signals which are responsible for mediating these effects. We show that activation of phospholipase C may affect APP processing by either of two pathways, one involving an increase in protein kinase C and the other an increase in cytoplasmic calcium levels. The effects of calcium on APP processing appear to be independent of protein kinase C activation. The observed effects of calcium on APP processing may be of therapeutic utility.

The survival of developing neurons: A review of afferent control

Developmental cell death is a major event of neurogenesis, and emphasis has systematically been placed on the roles of either the peripheral targets or central postsynaptic neurons in the control of neuronal survival. In this article, the main types of experimental design used to test the control of neuronal death by the afferent supply are compared with analogous data indicating neurotrophic support by the targets. It is argued that targets and afferents may have equivalent roles and interact in the control of neuron numbers during development of the vertebrate nervous system. Possible mechanisms of anterograde trophic control include contact-mediated cell interactions, activity-dependent processes mediated by neurotransmitters or neuromodulators, modulation of the levels of cytoplasmic free calcium and the involvement of neurotrophic factors.