Journal article
Seizure Termination by Acidosis Depends on ASIC1a
Nature neuroscience, Vol.11(7), pp.816-822
07/2008
DOI: 10.1038/nn.2132
PMCID: PMC2553357
PMID: 18536711
Abstract
Most seizures stop spontaneously. However, the molecular mechanisms remain unknown. Earlier observations that seizures reduce brain pH and that acidosis inhibits seizures indicated that acidosis halts epileptic activity. Because acid–sensing ion channel–1a (ASIC1a) shows exquisite sensitivity to extracellular pH and regulates neuron excitability, we hypothesized that acidosis might activate ASIC1a to terminate seizures. Disrupting mouse ASIC1a increased the severity of chemoconvulsant–induced seizures, whereas overexpressing ASIC1a had the opposite effect. ASIC1a did not affect seizure threshold or onset, but shortened seizure duration and prevented progression. CO2 inhalation, long known to lower brain pH and inhibit seizures, also required ASIC1a to interrupt tonic–clonic seizures. Acidosis activated inhibitory interneurons through ASIC1a, suggesting that ASIC1a might limit seizures by increasing inhibitory tone. These findings identify ASIC1a as a key element in seizure termination when brain pH falls. The results suggest a molecular mechanism for how the brain stops seizures and suggest new therapeutic strategies.
Details
- Title: Subtitle
- Seizure Termination by Acidosis Depends on ASIC1a
- Creators
- Adam E Ziemann - Department of Veterans Affairs Medical Center, Iowa City, IA, 52242Mikael K Schnizler - Department of Veterans Affairs Medical Center, Iowa City, IA, 52242Gregory W Albert - Department of Veterans Affairs Medical Center, Iowa City, IA, 52242Meryl A Severson - Department of Veterans Affairs Medical Center, Iowa City, IA, 52242Matthew A Howard - Department of Veterans Affairs Medical Center, Iowa City, IA, 52242Michael J Welsh - Department of Veterans Affairs Medical Center, Iowa City, IA, 52242John A Wemmie - Department of Veterans Affairs Medical Center, Iowa City, IA, 52242
- Resource Type
- Journal article
- Publication Details
- Nature neuroscience, Vol.11(7), pp.816-822
- DOI
- 10.1038/nn.2132
- PMID
- 18536711
- PMCID
- PMC2553357
- NLM abbreviation
- Nat Neurosci
- ISSN
- 1097-6256
- eISSN
- 1546-1726
- Language
- English
- Date published
- 07/2008
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute; Neurosurgery; Otolaryngology; Internal Medicine
- Record Identifier
- 9984003973102771
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