Annals of neurology
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Annals of neurology · Apr 2014
KCNT1 gain of function in 2 epilepsy phenotypes is reversed by quinidine.
Mutations in KCNT1 have been implicated in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and epilepsy of infancy with migrating focal seizures (EIMFS). More recently, a whole exome sequencing study of epileptic encephalopathies identified an additional de novo mutation in 1 proband with EIMFS. We aim to investigate the electrophysiological and pharmacological characteristics of hKCNT1 mutations and examine developmental expression levels. ⋯ These results establish direction for a targeted therapy and potentially exemplify a translational paradigm for in vitro studies informing novel therapies in a neuropsychiatric disease.
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Annals of neurology · Apr 2014
Botulinum toxin-A treatment reduces human mechanical pain sensitivity and mechanotransduction.
The mechanisms underlying the analgesic effects of botulinum toxin serotype A (BoNT-A) are not well understood. We have tested the hypothesis that BoNT-A can block nociceptor transduction. ⋯ In cultured rodent primary sensory neurons, BoNT-A decreased the proportion of neurons expressing slowly adapting mechanically gated currents linked to mechanical pain transduction. Inhibition of mechanotransduction provides a novel locus of action of BoNT-A, further understanding of which may extend its use as an analgesic agent.