Regional and subunit-specific downregulation of acid-sensing ion channels in the pilocarpine model of epilepsy.
Acid-sensing ion channels (ASICs) constitute a recently discovered family of excitatory cation channels, structurally related to the superfamily of degenerin/epithelial sodium channels. ASIC1b and ASIC3 are highly expressed in primary sensory neurons and are thought to play a role in pain transmission related to acidosis. ASIC1a, ASIC2a, and ASIC2b are also distributed in the central nervous system where their function remains unclear. We investigated here the regulation of their expression during status epilepticus (SE), a condition in which neuronal overexcitation leads to acidosis. In animals treated with pilocarpine (380 mg/kg) to induce SE, we observed a marked decrease of ASIC2b mRNA levels in all hippocampal areas and of ASIC1a mRNA levels in the CA1-2 fields. These changes were also observed after protective treatment from neuronal cell death with diazepam (10 mg/kg) and pentobarbital (30 mg/kg). These findings suggest a key role of channels containing ASIC1a and ASIC2b subunits in both normal and pathological activity of hippocampus.
Biagini
G
G
Department of Neurology and Neurosurgery, and Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A2B4, Canada.
Babinski
K
K
Avoli
M
M
Marcinkiewicz
M
M
Séguéla
P
P
D062565:Acid Sensing Ion Channels; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D003292:Convulsants / Q000494:pharmacology*; D015342:DNA Probes; D015536:Down-Regulation / Q000502:physiology*; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D007473:Ion Channels / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000473:pathology; D010862:Pilocarpine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000378:metabolism
C568266:ASIC1 protein, human; C112231:ASIC3 protein, human; C568269:ASIC3 protein, rat; D062565:Acid Sensing Ion Channels; D003292:Convulsants; D015342:DNA Probes; D007473:Ion Channels; D008565:Membrane Proteins; D018721:Muscarinic Agonists; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D015222:Sodium Channels; D010862:Pilocarpine