Calcium-dependent inactivation of high-threshold calcium currents in human dentate gyrus granule cells

Authors


Corresponding author I. Mody: Departments of Neurology and Physiology, UCLA School of Medicine, 710 Westwood Plaza, Los Angeles, CA 90095-176, USA. Email: mody@ucla.edu

Abstract

  • 1Dentate gyrus granule cells acutely dissociated from hippocampal slices obtained from chronic temporal lobe epilepsy (TLE) patients displayed a high-voltage activated (HVA) Ca2+ conductance with a pronounced Ca2+-dependent inactivation.
  • 2Inactivation time constants and peak HVA Ca2+ current (ICa) amplitudes did not differ between perforated patch and whole-cell recordings without added exogenous Ca2+ buffers, indicating that the Ca2+-dependent characteristics of ICa inactivation were well preserved in whole-cell recordings.
  • 3Inactivation time constants correlated with whole-cell ICa, and were increased when Ca2+ was replaced with Ba2+ in the external solution or 5 mm BAPTA was added to the pipette solution.
  • 4In recordings without added exogenous Ca2+ buffers, the time course of ICa inactivation was comparable between human TLE and kindled rat granule cells. Conversely, the time course of ICa in human TLE granule cells loaded with 5 mm intracellular BAPTA resembled that observed in buffer-free recordings from control rat neurones.
  • 5The loss of a putative intraneuronal Ca2+ buffer, the Ca2+-binding protein calbindin (CB), from human granule cells during TLE may result in the pronounced Ca2+-dependent ICa inactivation. This process could serve a neuroprotective role by significantly decreasing Ca2+ entry during prolonged trains of action potentials known to occur during seizures.

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