Linked Life Data

21451059

Source:http://linkedlifedata.com/resource/pubmed/id/21451059

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-7-4
pubmed:abstractText
There is clinical need to extend the understanding of epilepsy and to find novel approaches to treat this condition. Bang-sensitive (bs) Drosophila mutants, which exhibit reduced thresholds for seizure, offer an attractive possibility to combine tractable genetics, electrophysiology, and high-throughput screening. However, despite these advantages, the precise electrophysiological aberrations that contribute to seizure have not been identified in any bs mutant. Because of this, the applicability of Drosophila as a preclinical model has not yet been established. In this study, we show that electroshock of bs slamdance (sda) larvae was sufficient to induce extended seizure-like episodes. Whole cell voltage-clamp recordings from identified motoneurons (termed aCC and RP2) showed synaptic currents that were greatly increased in both amplitude and duration. Current-clamp recordings indicated that these inputs produced longer-lived plateau depolarizations and increased action potential firing in these cells. An analysis of voltage-gated currents in these motoneurons, in both first and third instar larvae, revealed a consistently increased persistent Na(+) current (I(Nap)) and a reduced Ca(2+) current in first instar larvae, which appeared normal in older third instar larvae. That increased I(Nap) may contribute to seizure-like activity is indicated by the observation that feeding sda larvae the antiepileptic drug phenytoin, which was sufficient to reduce I(Nap), rescued both seizure-like episode duration and synaptic excitation of motoneurons. In contrast, feeding of either anemone toxin, a drug that preferentially increases I(Nap), or phenytoin to wild-type larvae was sufficient to induce a bs behavioral phenotype. Finally, we show that feeding of phenytoin to gravid sda females was sufficient to both reduce I(Nap) and synaptic currents and rescue the bs phenotype in their larval progeny, indicating that a heightened predisposition to seizure may arise as a consequence of abnormal embryonic neural development.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1522-1598
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
106
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18-29
pubmed:meshHeading
pubmed-meshheading:21451059-Action Potentials, pubmed-meshheading:21451059-Animals, pubmed-meshheading:21451059-Anticonvulsants, pubmed-meshheading:21451059-Calcium Channels, pubmed-meshheading:21451059-Cnidarian Venoms, pubmed-meshheading:21451059-Disease Models, Animal, pubmed-meshheading:21451059-Drosophila Proteins, pubmed-meshheading:21451059-Drosophila melanogaster, pubmed-meshheading:21451059-Electroshock, pubmed-meshheading:21451059-Epilepsy, Reflex, pubmed-meshheading:21451059-Female, pubmed-meshheading:21451059-Genetic Predisposition to Disease, pubmed-meshheading:21451059-Larva, pubmed-meshheading:21451059-Motor Neurons, pubmed-meshheading:21451059-Mutation, pubmed-meshheading:21451059-Noise, pubmed-meshheading:21451059-Phenytoin, pubmed-meshheading:21451059-Seizures, pubmed-meshheading:21451059-Sodium Channels
pubmed:year
2011
pubmed:articleTitle
Increased persistent Na+ current contributes to seizure in the slamdance bang-sensitive Drosophila mutant.
pubmed:affiliation
Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't