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

29 Citations (Scopus)

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

Fingerprint

Febrile Seizures
Pyramidal Cells
Temperature
Nimodipine
Sodium Channel Blockers
L-Type Calcium Channels
Carbamazepine
Gadolinium
Brain
Phenytoin
Knockout Mice
Anticonvulsants
Sodium
L-type calcium channel alpha(1C)
Pharmacology
Polymerase Chain Reaction
Incidence
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Radzicki, Daniel ; Yau, Hau Jie ; Pollema-Mays, Sarah L. ; Mlsna, Lauren ; Cho, Kangho ; Koh, Sookyong ; Martina, Marco. / Temperature-sensitive Cav1.2 calcium channels support intrinsic firing of pyramidal neurons and provide a target for the treatment of febrile seizures. In: Journal of Neuroscience. 2013 ; Vol. 33, No. 24. pp. 9920-9931.
@article{a0862754bef941d8a8106f1cc967d89b,
title = "Temperature-sensitive Cav1.2 calcium channels support intrinsic firing of pyramidal neurons and provide a target for the treatment of febrile seizures",
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.",
author = "Daniel Radzicki and Yau, {Hau Jie} and Pollema-Mays, {Sarah L.} and Lauren Mlsna and Kangho Cho and Sookyong Koh and Marco Martina",
year = "2013",
month = "6",
day = "17",
doi = "10.1523/JNEUROSCI.5482-12.2013",
language = "English (US)",
volume = "33",
pages = "9920--9931",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "24",

}

Temperature-sensitive Cav1.2 calcium channels support intrinsic firing of pyramidal neurons and provide a target for the treatment of febrile seizures. / Radzicki, Daniel; Yau, Hau Jie; Pollema-Mays, Sarah L.; Mlsna, Lauren; Cho, Kangho; Koh, Sookyong; Martina, Marco.

In: Journal of Neuroscience, Vol. 33, No. 24, 17.06.2013, p. 9920-9931.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Temperature-sensitive Cav1.2 calcium channels support intrinsic firing of pyramidal neurons and provide a target for the treatment of febrile seizures

AU - Radzicki, Daniel

AU - Yau, Hau Jie

AU - Pollema-Mays, Sarah L.

AU - Mlsna, Lauren

AU - Cho, Kangho

AU - Koh, Sookyong

AU - Martina, Marco

PY - 2013/6/17

Y1 - 2013/6/17

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84878876322&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878876322&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.5482-12.2013

DO - 10.1523/JNEUROSCI.5482-12.2013

M3 - Article

C2 - 23761887

AN - SCOPUS:84878876322

VL - 33

SP - 9920

EP - 9931

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 24

ER -