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

Abstract

1. Dentate 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. 2. Inactivation 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. 3. Inactivation 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. 4. In 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. 5. The 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.