Abstract
Amyotrophic lateral sclerosis is characterized by motoneuron degeneration, in which glutamate-induced cell death is thought to play a pathogenic role. This excitotoxic process is mediated by cytosolic Ca2+ overload. The glutamatergic ionotropic channel molecules, which constitute a major route of Ca2+ entry, were present on cultured spinal motoneurons. Using ratio RT-PCR, the relative presence in isolated motoneurons of the GluR subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor was evaluated. GluR1 and GluR2 mRNAs were present abundantly, while GluR3 and GluR4 mRNAs were much less abundant. The relative amount of mRNAs encoding the different protein isoforms responsible for Ca2+ uptake into the internal stores and for controlled release of Ca2+ from these stores was also determined. For the sarco/endoplasmic reticulum Ca2+ ATPases (SERCAs), only the SERCA2b class 4 splice variant was found. The inositol 1,4,5-trisphosphate receptor (IP3R) mRNAs were mainly transcribed from the IP3RI and IP3RII genes. Heterogeneity was also observed for the ryanodine receptors (RyR) as the RyR1, RyR2 and RyR3 mRNAs were present.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium / antagonists & inhibitors
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Calcium / metabolism*
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Calcium Channels / biosynthesis
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Calcium Channels / genetics
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Calcium Channels / metabolism
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Calcium-Transporting ATPases / biosynthesis
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Calcium-Transporting ATPases / genetics
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Calcium-Transporting ATPases / metabolism
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Cells, Cultured
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Endoplasmic Reticulum / enzymology
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Inositol 1,4,5-Trisphosphate Receptors
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Kainic Acid / pharmacology
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Motor Neurons / drug effects
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Motor Neurons / metabolism*
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Nerve Tissue Proteins / biosynthesis
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Nerve Tissue Proteins / physiology
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Protein Isoforms
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RNA, Messenger / metabolism
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Rats
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Receptors, AMPA / biosynthesis
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Receptors, AMPA / genetics
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Receptors, AMPA / metabolism
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Receptors, AMPA / physiology
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Receptors, Cytoplasmic and Nuclear / biosynthesis
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism
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Ryanodine Receptor Calcium Release Channel / biosynthesis
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Ryanodine Receptor Calcium Release Channel / genetics
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Ryanodine Receptor Calcium Release Channel / metabolism
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Sarcoplasmic Reticulum / enzymology
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Spinal Cord / cytology*
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Spinal Cord / drug effects
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology
Substances
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Calcium Channels
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Inositol 1,4,5-Trisphosphate Receptors
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Nerve Tissue Proteins
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Protein Isoforms
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RNA, Messenger
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Receptors, AMPA
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Receptors, Cytoplasmic and Nuclear
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Ryanodine Receptor Calcium Release Channel
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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Calcium-Transporting ATPases
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Kainic Acid
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Calcium