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Ca2+ Accumulation (ca2+ + accumulation)
Selected AbstractsContribution of T-type VDCC to TEA-induced long-term synaptic modification in hippocampal CA1 and dentate gyrusHIPPOCAMPUS, Issue 5 2002Dong Song Abstract We have previously reported that exposure to the K+ channel blocker tetraethylammonium (TEA), 25 mM, induces long-term potentiation (LTP) in CA1, but not in the dentate gyrus (DG), of the rat hippocampal slice. During TEA application, stimulation of excitatory afferents results in a strong depolarizing potential after the fast excitatory postsynaptic potential (EPSP) in CA1, but not in DG. We hypothesized that the differential effect of TEA on long-term synaptic modification in CA1 and DG results from different levels of TEA-elicited depolarization in the two cell types. Additional pharmacological studies showed that blockade of T-type voltage-dependent calcium channels (VDCCs) decreased both the magnitude of LTP and the late, depolarizing potential in CA1. Blockade of L-type VDCCs had no such effect. Using computer models of morphologically reconstructed CA1 pyramidal cells and DG granule cells, we tested our hypothesis by simulating the relative intracellular Ca2+ accumulation and membrane potential changes mediated by T-type and L-type VDCCs. Simulation results using pyramidal cell models showed that, with decreased maximum conductance of TEA-sensitive potassium channels, synaptic inputs elicited strong depolarizing potentials similar to those observed with intracellular recording. During this depolarization, VDCCs were opened and resulted in a large intracellular Ca2+ accumulation that presumably caused LTP. When T-type VDCCs were blocked, the magnitudes of both the Ca2+ accumulation and the late depolarizing potential were decreased substantially. Simulated blockade of L-type VDCCs had only a minor effect. Together, our modeling and experimental studies indicate that T-type VDCCs, rather than L-type VDCCs, are primarily responsible for facilitating the depolarizing potential caused by TEA and for the consequent Ca2+ influx. Thus, our findings strongly suggest that the induction of TEA-LTP in CA1 depends primarily on T-type, rather than L-type, VDCCs. Simulation results using modeled granule cells suggests that the failure of TEA to induce LTP in DG is partly due to a low density of T-type VDCCs in granule cell membranes. Hippocampus 2002;12:689,697. © 2002 Wiley-Liss, Inc. [source] Involvement of Ca2+ and ROS in ,-tocopheryl succinate-induced mitochondrial permeabilizationINTERNATIONAL JOURNAL OF CANCER, Issue 8 2010Vladimir Gogvadze Abstract Release of mitochondrial proteins such as cytochrome c, AIF, Smac/Diablo etc., plays a crucial role in apoptosis induction. A redox-silent analog of vitamin E, ,-tocopheryl succinate (,-TOS), was shown to stimulate cytochrome c release via production of reactive oxygen species (ROS) and Bax-mediated permeabilization of the outer mitochondrial membrane. Here we show that ,-TOS facilitates mitochondrial permeability transition (MPT) in isolated rat liver mitochondria, Tet21N neuroblastoma cells and Jurkat T-lymphocytes. In particular, in addition to ROS production, ,-TOS stimulates rapid Ca2+ entry into the cells with subsequent accumulation of Ca2+ in mitochondria,a prerequisite step for MPT induction. Alteration of mitochondrial Ca2+ buffering capacity was observed as early as 8 hr after incubation with ,-TOS, when no activation of Bax was yet detected. Ca2+ accumulation in mitochondria was important for apoptosis progression, since inhibition of mitochondrial Ca2+ uptake significantly mitigated the apoptotic response. Importantly, Ca2+ -induced mitochondrial destabilization might cooperate with Bax-mediated mitochondrial outer membrane permeabilization to induce cytochrome c release from mitochondria. [source] Glutamate-induced calcium increase mediates magnesium release from mitochondria in rat hippocampal neuronsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 14 2010Yutaka Shindo Abstract Excess administration of glutamate is known to induce Ca2+ overload in neurons, which is the first step in excitotoxicity. Although some reports have suggested a role for Mg2+ in the excitotoxicity, little is known about its actual contribution. To investigate the role of Mg2+ in the excitotoxicity, we simultaneously measured intracellular Ca2+ and Mg2+, using fluorescent dyes, Fura red, a fluorescent Ca2+ probe, and KMG-104, a highly selective fluorescent Mg2+ probe developed by our group, respectively. Administration of 100 ,M glutamate supplemented with 10 ,M glycine to rat hippocampal neurons induced an increase in intracellular Mg2+ concentration ([Mg2+]i). Extracellular Mg2+ was not required for this glutamate-induced increase in [Mg2+]i, and no increase in intracellular Ca2+ concentration ([Ca2+]i) or [Mg2+]i was observed in neurons in nominally Ca2+ -free medium. Application of 5 ,M carbonyl cyanide p -(trifluoromethoxy) phenylhydrazone (FCCP), an uncoupler of mitochondrial inner membrane potential, also elicited increases in [Ca2+]i and [Mg2+]i. Subsequent administration of glutamate and glycine following FCCP treatment did not induce a further increase in [Mg2+]i but did induce an additive increase in [Ca2+]i. Moreover, the glutamate-induced increase in [Mg2+]i was observed only in mitochondria localized areas. These results support the idea that glutamate is able to induced Mg2+ efflux from mitochondria to the cytosol. Furthermore, pretreatment with Ru360, an inhibitor of the mitochondrial Ca2+ uniporter, prevented this [Mg2+]i increase. These results indicate that glutamate-induced increases in [Mg2+]i result from the Mg2+ release from mitochondria and that Ca2+ accumulation in the mitochondria is required for this Mg2+ release. © 2010 Wiley-Liss, Inc. [source] The potato StLTPa7 gene displays a complex Ca2+ -associated pattern of expression during the early stage of potato,Ralstonia solanacearum interactionMOLECULAR PLANT PATHOLOGY, Issue 1 2009GANG GAO SUMMARY Although nonspecific lipid transfer proteins (nsLTPs) are widely expressed during plant defence responses to pathogens, their functions and regulation are not fully understood. In this article, we report the isolation of a cDNA for the new nsLTP, StLTPa7, from cultivated potato (Solanum tuberosum) infected with Ralstonia solanacearum. The cDNA was predicted to encode a type 1 nsLTP containing an N-terminal signal sequence and possessing the characteristic features of nsLTPs. A phylogenetic analysis showed that the encoded amino acid sequence of the nsLTP was similar to those of other previously reported plant nsLTPs, which contain a putative calmodulin-binding site consisting of approximately 12 highly conserved amino acid residues. The expression of the StLTPa7 gene was studied during the early stages of potato,R. solanacearum interaction using real-time quantitative polymerase chain reaction (qRT-PCR) and Northern analyses, and a complex calcium (Ca2+)-associated pattern of expression was observed with the following features: (i) transcripts of the StLTPa7 gene were systemically up-regulated by infection with R. solanacearum; (ii) the StLTPa7 gene was stimulated by salicylic acid, methyl jasmonate, abscisic acid and Ca2+; (iii) qRT-PCR showed that, during the early stage of R. solanacearum infection, nsLTP transcripts accumulated over a time course that paralleled that of Ca2+ accumulation, detected using environmental scanning electron microscopy and energy-dispersive X-ray (EDAX) spectrometry; and (iv) the Ca2+ channel blocker, ruthenium red, partially blocked R. solanacearum -induced StLTPa7 expression. This report represents the first use of EDAX analysis to establish a synchrony between Ca2+ accumulation and nsLTP expression in response to potato,R. solanacearum interactions. Collectively, these results suggest that StLTPa7 may be a pathogen- and Ca2+ -responsive plant defence gene. [source] Glutamate receptors on myelinated spinal cord axons: I. GluR6 kainate receptors,ANNALS OF NEUROLOGY, Issue 2 2009Mohamed Ouardouz PhD Objective The deleterious effects of glutamate excitotoxicity are well described for central nervous system gray matter. Although overactivation of glutamate receptors also contributes to axonal injury, the mechanisms are poorly understood. Our goal was to elucidate the mechanisms of kainate receptor,dependent axonal Ca2+ deregulation. Methods Dorsal column axons were loaded with a Ca2+ indicator and imaged in vitro using confocal laser-scanning microscopy. Results Activation of glutamate receptor 6 (GluR6) kainate receptors promoted a substantial increase in axonal [Ca2+]. This Ca2+ accumulation was due not only to influx from the extracellular space, but a significant component originated from ryanodine-dependent intracellular stores, which, in turn, depended on activation of L-type Ca2+ channels: ryanodine, nimodipine, or nifedipine blocked the agonist-induced Ca2+ increase. Also, GluR6 stimulation induced intraaxonal production of nitric oxide (NO), which greatly enhanced the Ca2+ response: quenching of NO with intraaxonal (but not extracellular) scavengers, or inhibition of neuronal NO synthase with intraaxonal N,-nitro-L-arginine methyl ester, blocked the Ca2+ increase. Loading axons with a peptide that mimics the C-terminal PDZ binding sequence of GluR6, thus interfering with the coupling of GluR6 to downstream effectors, greatly reduced the agonist-induced axonal Ca2+ increase. Immunohistochemistry showed GluR6/7 clusters on the axolemma colocalized with neuronal NO synthase and Cav1.2. Interpretation Myelinated spinal axons express functional GluR6-containing kainate receptors, forming part of novel signaling complexes reminiscent of postsynaptic membranes of glutamatergic synapses. The ability of such axonal "nanocomplexes" to release toxic amounts of Ca2+ may represent a key mechanism of axonal degeneration in disorders such as multiple sclerosis where abnormal accumulation of glutamate and NO are known to occur. Ann Neurol 2009 [source] | |||||||||||||