Carbamazepine effects on Na+ currents in human dentate granule cells from epileptogenic tissue

G Reckziegel1, H Beck, J Schramm

  • 1Department of Epileptology, University of Bonn Medical Center, Germany.

Epilepsia
|April 29, 1999
PubMed
Abstract

Insights

Carbamazepine (CBZ) affects sodium channel inactivation in human epilepsy neurons, but not recovery from inactivation. This may explain why some temporal lobe epilepsy (TLE) cases are medically intractable.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Epilepsy Research

Background:

  • Carbamazepine (CBZ) is a standard treatment for temporal lobe epilepsy (TLE).
  • CBZ's anticonvulsant effects are linked to voltage-dependent sodium (Na+) channels.
  • Its action on human neurons in focal epilepsy remains unclear.

Purpose of the Study:

  • Investigate CBZ's effects on Na+ currents in human TLE neurons.
  • Determine if human TLE neurons respond similarly to nonhuman models.

Main Methods:

  • Whole-cell patch-clamp technique.
  • Studied acutely isolated dentate granule cells (DGCs) from TLE patients.
  • Examined effects of CBZ on voltage-dependent Na+ currents.

Main Results:

  • CBZ reduced Na+ current amplitude and shifted steady-state inactivation hyperpolarizing.
  • CBZ did not affect the rapid component of Na+ current recovery from inactivation.
  • Repetitive stimulation effects on Na+ current amplitude were not significantly altered by CBZ.

Conclusions:

  • CBZ significantly impacts steady-state inactivation of human DGC Na+ currents.
  • CBZ does not affect the removal of inactivation in these neurons.
  • CBZ insensitivity in Na+ current recovery may explain medically intractable TLE.