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

Journal of Neurophysiology
Fu-Wen Zhou, Steven N Roper

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 t...Continue Reading

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Citations

Sep 24, 2020·Oxidative Medicine and Cellular Longevity·Rui WangAnwen Shao
May 28, 2020·Frontiers in Physiology·Daniele Maria-FerreiraElizabeth Soares Fernandes
Mar 23, 2021·Frontiers in Cell and Developmental Biology·Kihwan LeeChul-Kyu Park
Jun 21, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Pavan ThapakShyam S Sharma

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