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

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Abstract
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. 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. 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. 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. 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.