Temperature-sensitive Cav1.2 calcium channels support intrinsic firing of pyramidal neurons and provide a target for the treatment of febrile seizures

Daniel Radzicki, Hau Jie Yau, Sarah L. Pollema-Mays, Lauren Mlsna, Kangho Cho, Sookyong Koh, Marco Martina*

*Corresponding author for this work

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Febrile seizures are associated with increased brain temperature and are often resistant to treatments with antiepileptic drugs, such as carbamazepine and phenytoin, which are sodium channel blockers. Although they are clearly correlated with the hyperthermic condition, the precise cellular mechanisms of febrile seizures remain unclear. We performed patch-clamp recordings from pyramidal cells in acute rat brain slices at temperatures up to 40°C and found that, at37°C, L-type calcium channels are active at unexpectedly hyperpolarized potentials and drive intrinsic firing, which is also supported by a temperature-dependent, gadolinium-sensitive sodium conductance. Pharmacological data, RT-PCR, and the current persistence in Cav1.3 knock-out mice suggested a critical contribution of Cav1.2 subunits to the temperature-dependent intrinsic firing, which was blocked by nimodipine. Because intrinsic firingmayplay a critical role in febrile seizures, we tested the effect of nimodipine in an in vivo model of febrile seizures and found that this drug dramatically reduces both the incidence and duration of febrile seizures in rat pups, suggesting new possibilities of intervention for this important pathological condition.

Original languageEnglish (US)
Pages (from-to)9920-9931
Number of pages12
JournalJournal of Neuroscience
Volume33
Issue number24
DOIs
StatePublished - Jun 17 2013

ASJC Scopus subject areas

  • Neuroscience(all)

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