Regional and Subunit-Specific Downregulation of Acid-Sensing Ion Channels Following Pilocarpine-Induced Seizures
Abstract number :
1.142
Submission category :
Year :
2000
Submission ID :
3157
Source :
www.aesnet.org
Presentation date :
12/2/2000 12:00:00 AM
Published date :
Dec 1, 2000, 06:00 AM
Authors :
Kazimierz Babinski, Giuseppe Biagini, Martin Marcinkiewicz, Philippe Seguela, Massimo Avoli, Antalium Inc, Montreal, PQ, Canada; Montreal Neurological Institute, McGill Univ, Montreal, Canada; Clin Research Institute of Montreal, Montreal, Canada.
RATIONALE: Acid-sensing ion channels (ASIC) constitute a recently discovered family of proton-activated excitatory cation channels, structurally related to the degenerin/epithelial sodium channel superfamily of amiloride-sensitive ion channels. Six ASIC subunits have been cloned to date (ASIC1a, 1b, 2a, 2b, 3 and 4). Their functions in the CNS are still unclear and might include neurotransmission and nociception. To gain better insight, we studied the mRNA distribution of ASIC subunits by Northern blot and in situ hybridization in rat neonatal whole-body sections and adult brain, and investigated their expression following pilocarpine-induced seizures. METHODS: Two-day and 2-month old normal rats were used. Five treatment groups were employed to document the effects of pilocarpine-induced seizures (n=3-8/group): controls; convulsive pilocarpine (380 mg/kg/ml); subconvulsive pilocarpine (200 mg/kg/ml); convulsive pilocarpine followed by diazepam (10 mg/kg/ml) + pentobarbital (30 mg/kg/ml), 30 min after status epilepticus; and diazepam + pentobarbital alone. RESULTS: In neonates, ASIC subunits were expressed in the nervous tissue as well as in the skin, stomach, liver, bone, submaxillary gland, seminal vesicles. In the adult, ASIC1a was almost uniformly distributed in all brain areas. In contrast, ASIC2a was highly expressed in medial habenula, triangular septal nucleus and zona incerta, ASIC2b in the CA3 hippocampal field, and ASIC4 in the neostriatum. Medium to low mRNA levels were found for each subunit in the other brain regions. ASIC1b and 3 were expressed at high level only in dorsal root ganglia. After seizures, ASIC1a and ASIC2b were downregulated to 50% of basal values in the CA1 area, with ASIC2B levels also decreasing in the other hippocampal regions. Similar results were found in rats, which received diazepam+pentobarbital alone, indicating that cell death was not the cause of downregulation. CONCLUSIONS: :These findings indicate that specific ASIC subunits might play a role in the response of limbic structures to pilocarpine-induced seizures.