TRPC3 mediates hyperexcitability and epileptiform activity in immature cortex and experimental cortical dysplasia

Fuwen Zhou, Steven N. Roper

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Neuronal hyperexcitability plays an important role in epileptogenesis. Conditions of low extracellular calcium (Ca) or magnesium (Mg) can induce hyperexcitability and epileptiform activity with unclear mechanisms. Transient receptor potential canonical type 3 (TRPC3) channels play a pivotal role in neuronal excitability and are activated in low-Ca and/or low-Mg conditions to depolarize neurons. TRPC3 staining was highly enriched in immature, but very weak in mature, control cortex, whereas it was strong in dysplastic cortex at all ages. Depolarization and susceptibility to epileptiform activity increased with decreasing Ca and Mg. Combinations of low Ca and low Mg induced larger depolarization in pyramidal neurons and greater susceptibility to epileptiform activity in immature and dysplastic cortex than in mature and control cortex, respectively. Intracellular application of anti- TRPC3 antibody to block TRPC3 channels and bath application of the selective TRPC3 inhibitor Pyr3 greatly diminished depolarization in immature control and both immature and mature dysplastic cortex with strong TRPC3 expression. Epileptiform activity was initiated in low Ca and low Mg when synaptic activity was blocked, and Pyr3 completely suppressed this activity. In conclusion, TRPC3 primarily mediates low Ca- and low Mg-induced depolarization and epileptiform activity, and the enhanced expression of TRPC3 could make dysplastic and immature cortex more hyperexcitable and more susceptible to epileptiform activity.

Original languageEnglish (US)
Pages (from-to)1227-1237
Number of pages11
JournalJournal of Neurophysiology
Volume111
Issue number6
DOIs
StatePublished - Mar 15 2014

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Malformations of Cortical Development
Magnesium
Calcium
Pyramidal Cells
Baths
Staining and Labeling
Neurons
Antibodies

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Physiology

Cite this

TRPC3 mediates hyperexcitability and epileptiform activity in immature cortex and experimental cortical dysplasia. / Zhou, Fuwen; Roper, Steven N.

In: Journal of Neurophysiology, Vol. 111, No. 6, 15.03.2014, p. 1227-1237.

Research output: Contribution to journalArticle

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