Calcium-dependent inactivation of high-threshold calcium currents in human dentate gyrus granule cells.
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.
Nagerl
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UV
Departments of Neurology and Physiology, UCLA School of Medicine, 710 Westwood Plaza, Los Angeles, CA 90095-176, USA.
Mody
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D000328:Adult; D000818:Animals; D001464:Barium / Q000494:pharmacology; D064026:Calbindins; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
D064026:Calbindins; D015220:Calcium Channels; D002614:Chelating Agents; D009419:Nerve Tissue Proteins; D064030:S100 Calcium Binding Protein G; D001464:Barium; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium