Linked Life Data

16949760

Source:http://linkedlifedata.com/resource/pubmed/id/16949760

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2006-11-1
pubmed:abstractText
AMPA-type glutamate receptor (GluR) channels provide fast excitatory synaptic transmission in the CNS, but mediate also cytotoxic insults. It could be shown that AMPA-type GluR channel-mediated chronic excitotoxicity leads to an increased intracellular calcium concentration and plays an important role in neurodegenerative diseases like for example amyotrophic lateral sclerosis (ALS). As calcium is an important mediator of various processes in the cell and calcium signals have to be very precise in the temporospatial resolution, excessive intracellular calcium increases can seriously impair cell function. It is still unclear if AMPA-type receptors can directly interact with the intracellular calcium homeostasis or if other mechanisms are involved in this process. The objective of this study was therefore to investigate the calcium homeostasis in rat motoneurons under physiological stimulation of AMPA-type GluR channels using calcium imaging techniques and patch-clamp recordings simultaneously. It was found that spontaneous excitatory postsynaptic currents of cultured motoneurons did not elicit significant intracellular calcium transients. Large intracellular calcium transients occurred only when preceding fast sodium currents were observed. Pharmacological experiments showed that activation of AMPA-type GluR channels during synaptic transmission has a great functional impact on the calcium homeostasis in motoneurons as all kinds of activity was completely blocked by application of the selective kainate- and AMPA-type GluR channel blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Furthermore we suggest from our experiments that calcium transients of several hundred milliseconds' duration result from release of calcium from the endoplasmic reticulum via activation of ryanodine receptors (calcium-induced calcium release, CICR). Our results help to understand the regulatory function of AMPA-type GluR channels in the intracellular calcium homeostasis which is known to be disturbed in neurodegenerative diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
142
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1019-29
pubmed:meshHeading
pubmed-meshheading:16949760-Amyotrophic Lateral Sclerosis, pubmed-meshheading:16949760-Animals, pubmed-meshheading:16949760-Calcium, pubmed-meshheading:16949760-Calcium Channels, pubmed-meshheading:16949760-Calcium Signaling, pubmed-meshheading:16949760-Cells, Cultured, pubmed-meshheading:16949760-Coculture Techniques, pubmed-meshheading:16949760-Endoplasmic Reticulum, pubmed-meshheading:16949760-Excitatory Amino Acid Antagonists, pubmed-meshheading:16949760-Excitatory Postsynaptic Potentials, pubmed-meshheading:16949760-Glutamic Acid, pubmed-meshheading:16949760-Motor Neurons, pubmed-meshheading:16949760-Nerve Net, pubmed-meshheading:16949760-Neural Pathways, pubmed-meshheading:16949760-Neurotoxins, pubmed-meshheading:16949760-Patch-Clamp Techniques, pubmed-meshheading:16949760-Rats, pubmed-meshheading:16949760-Receptors, AMPA, pubmed-meshheading:16949760-Ryanodine Receptor Calcium Release Channel, pubmed-meshheading:16949760-Sodium Channels, pubmed-meshheading:16949760-Spinal Cord, pubmed-meshheading:16949760-Synaptic Transmission, pubmed-meshheading:16949760-Time Factors
pubmed:year
2006
pubmed:articleTitle
Temporospatial coupling of networked synaptic activation of AMPA-type glutamate receptor channels and calcium transients in cultured motoneurons.
pubmed:affiliation
Department of Neurology, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, OE 7210 Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't