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Intracellular Ca2+ Elevation (intracellular + ca2+_elevation)

Distribution by Scientific Domains
Medical Sciences50%

Selected Abstracts

Brain-derived neurotrophic factor induces long-lasting Ca2+ -activated K+ currents in rat visual cortex neurons

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2002
Yoshito Mizoguchi
Abstract Brain-derived neurotrophic factor (BDNF) increases postsynaptic intracellular Ca2+ and modulates synaptic transmission in various types of neurons. Ca2+ -activated K+ currents, opened mainly by intracellular Ca2+ elevation, contribute to hyperpolarization following action potentials and modulate synaptic transmission. We asked whether BDNF induces Ca2+ -activated K+ currents by postsynaptic elevation of intracellular Ca2+ in acutely dissociated visual cortex neurons of rats. Currents were analysed using the nystatin-perforated patch clamp technique and imaging of intracellular Ca2+ mobilization with fura-2. At a holding potential of ,50 mV, BDNF application (20 ng/mL) for 1,2 min induced an outward current (IBDNF-OUT; 80.0 ± 29.0 pA) lasting for more than 90 min without attenuation in every neuron tested. K252a (200 nm), an inhibitor of Trk receptor tyrosine kinase, and U73122 (3 ,m), a specific phospholipase C (PLC)-, inhibitor, suppressed IBDNF-OUT completely. IBDNF-OUT was both charybdotoxin- (600 nm) and apamin- (300 nm) sensitive, suggesting that this current was carried by Ca2+ -activated K+ channels. BAPTA-AM (150 ,m) gradually suppressed IBDNF-OUT. Fura-2 imaging revealed that a brief application of BDNF elicited a long-lasting elevation of intracellular Ca2+. These results show that BDNF induces long-lasting Ca2+ -activated K+ currents by sustained intracellular Ca2+ elevation in rat visual cortex neurons. While BDNF, likely acting through the Trk B receptor, was necessary for the induction of long-lasting Ca2+ -activated K+ currents via intracellular Ca2+ elevation, BDNF was not necessary for the maintenance of this current. [source]

Effects of sphingosine-1-phosphate and sphingosylphosphorylcholine on intracellular Ca2+ and cell death in prostate cancer cell lines

AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 4 2007
A. C. M. Mulders
Summary The sphingolipid metabolites sphingosine-1-phosphate (S1P) and sphingosylphosphorylcholine (SPC) can be involved in cellular growth and apoptosis, by both receptor-dependent and -independent mechanisms. We investigated the role of S1P and SPC in intracellular Ca2+ elevation, cell proliferation and cell death in DU 145 and PC3 hormone-refractory prostate cancer cell lines. S1P and SPC increased intracellular Ca2+ levels, most likely in a receptor-independent manner. Surprisingly, both S1P and SPC did not stimulate but rather reduced cell growth through induction of apoptosis. Therefore, antagonists targeted against S1P, SPC and their receptors do not appear to be promising new approaches in the treatment of hormone-refractory prostate cancer. [source]

Biological properties of a specific G,q/11 inhibitor, YM-254890, on platelet functions and thrombus formation under high-shear stress

BRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2006
Toshio Uemura
1The effects of YM-254890, a specific G,q/11 inhibitor, on platelet functions, thrombus formation under high-shear rate condition and femoral artery thrombosis in cynomolgus monkeys were investigated. 2YM-254890 concentration dependently inhibited ADP-induced intracellular Ca2+ elevation, with an IC50 value of 0.92±0.28 ,M. 3P-selectin expression induced by ADP or thrombin receptor agonist peptide (TRAP) was strongly inhibited by YM-254890, with IC50 values of 0.51±0.02 and 0.16±0.08 ,M, respectively. 4YM-254890 had no effect on the binding of fibrinogen to purified GPIIb/IIIa, but strongly inhibited binding to TRAP-stimulated washed platelets. 5YM-254890 completely inhibited platelet shape change induced by ADP, but not that induced by collagen, TRAP, arachidonic acid, U46619 or A23187. 6YM-254890 attenuated ADP-, collagen-, TRAP-, arachidonic acid- and U46619-induced platelet aggregation with IC50 values of <1 ,M, whereas it had no effect on phorbol 12-myristate 13-acetate-, ristocetin-, thapsigargin- or A23187-induced platelet aggregation. 7High-shear stress-induced platelet aggregation and platelet-rich thrombus formation on a collagen surface under high-shear flow conditions were concentration dependently inhibited by YM-254890. 8The antithrombotic effect of YM-254890 was evaluated in a model of cyclic flow reductions in the femoral artery of cynomolgus monkeys. The intravenous bolus injection of YM-254890 dose dependently inhibited recurrent thrombosis without affecting systemic blood pressure or prolonging template bleeding time. 9YM-254890 is a useful tool for investigating G,q/11 -coupled receptor signaling and the physiological roles of G,q/11. British Journal of Pharmacology (2006) 148, 61,69. doi:10.1038/sj.bjp.0706711 [source]

CXCL10-induced cell death in neurons: role of calcium dysregulation

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2006
Yongjun Sui
Abstract Chemokines play a key role in the regulation of central nervous system disease. CXCL10 over-expression has been observed in several neurodegenerative diseases, including multiple sclerosis, Alzheimer's disease and HIV-associated dementia. More recent studies by others and us have shown that CXCL10 elicits apoptosis in fetal neurons. The mechanism of CXCL10-mediated neurotoxicity, however, remains unclear. In this study, we provide evidence for the direct role of Ca2+ dysregulation in CXCL10-mediated apoptosis. We demonstrate that treatment of fetal neuronal cultures with exogenous CXCL10 produced elevations in intracellular Ca2+ and that this effect was modulated via the binding of CXCL10 to its cognate receptor, CXCR3. We further explored the association of intracellular Ca2+ elevations with the caspases that are involved in CXC10-induced neuronal apoptosis. Our data showed that increased Ca2+, which is available for uptake by the mitochondria, is associated with membrane permeabilization and cytochrome c release from this compartment. The released cytochrome c then activates the initiator active caspase-9. This initiator caspase sequentially activates the effector caspase-3, ultimately leading to apoptosis. This study identifies the temporal signaling cascade involved in CXCL10-mediated neuronal apoptosis and provides putative targets for pharmaceutical intervention of neurological disorders associated with CXCL10 up-regulation. [source]