T-type Ca2+ channel activity increases in rat hippocampal CA1 region during kindling epileptogenesis

Synapse. 2020 Sep;74(9):e22155. doi: 10.1002/syn.22155. Epub 2020 Apr 3.

Abstract

Epileptogenesis is a dynamical process that involves synaptic plasticity changes such as synaptic reorganization of excitatory and inhibitory systems and axonal sprouting in the hippocampus, which is one of the most studied epileptogenic regions in the brain. However, the early events that trigger these changes are not understood well. We investigated short-term and long-term synaptic plasticity parameters and T-type Ca2+ channel activity changes in the early phase of a rat kindling model. Chronic pentylenetetrazole (PTZ) application was used in order to induce the kindling process in rats. The recordings were obtained from hippocampal slices in the CA1 region at 25th day of PTZ application. Tetraethylammonium was used in order to induce long-term potentiation and T-type Ca2+ channel activity was assessed in the presence of mibefradil. We found that tetraethylammonium-induced long-term potentiation was not prevented by mibefradil in the kindling group in contrast to control group. We also found an increase in paired-pulse ratios in the PTZ-applied group. Our findings indicate an increase in the "T-type Ca2+ channel component of LTP" in the kindling group, which may be an early mechanism in epileptogenesis.

Keywords: T-type Ca2+ channels; epileptogenesis; hippocampus; kindling; synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / metabolism*
  • CA1 Region, Hippocampal / physiopathology
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, T-Type / metabolism*
  • Epilepsy / etiology
  • Epilepsy / metabolism*
  • Epilepsy / physiopathology
  • Long-Term Potentiation*
  • Male
  • Mibefradil / pharmacology
  • Pentylenetetrazole / toxicity
  • Rats
  • Rats, Wistar
  • Tetraethylammonium / pharmacology

Substances

  • Calcium Channel Blockers
  • Calcium Channels, T-Type
  • Mibefradil
  • Tetraethylammonium
  • Pentylenetetrazole