Properties of voltage-activated Ca2+ currents in acutely isolated human hippocampal granule cells.
Properties of Ba2+ currents through voltage-dependent Ca2+ channels (IBa) were investigated in 61 dentate granule cells acutely isolated from the resected hippocampus of nine patients with therapy-refractory temporal lobe epilepsy (TLE). Currents with a high threshold of activation (HVA) peaked at 0 mV, and showed some time-dependent inactivation and a voltage of half-maximal steady-state inactivation (V1/2inact) of -16.4 mV. Application of saturating doses of omega-conotoxin (omega-CgTx) GVIA or nifedipine distinguished characteristic N-type (38%) and L-type (62% of HVA currents) Ca2+ currents. Combined application of both agents blocked HVA currents by > 95%. In a 10-mo-old child but not in adult patients, an omega-agatoxin IVA (omega-AgaTxIVA)-sensitive but omega-CgTx MVIIC-insensitive, noninactivating component of HVA currents (approximately 24%) was present that most probably corresponds to a P-type current. A T-type Ca2+ current could be separated from HVA components on the basis of its steady-state voltage-dependent inactivation (V1/2inact = -71.0 mV). The T-type Ca2+ current isolated by subtraction peaked at more negative potentials (-10 mV), showed a significantly more rapid time-dependent inactivation, and could be selectively blocked by low concentrations of Ni2+. It was insensitive to nifedipine and omega-CgTx GVIA. We conclude that L-, N-, and T-type currents are present in adult human dentate granule cells and an additional P-type current is present in neurons from a 10-mo-old patient. These data may provide a basis for comparison with animal models of epilepsy and for the elucidation of mechanisms of action of drugs intended for use in human disease.
Beck
H
H
Department of Epileptology, University of Bonn Medical Center, Germany.
Steffens
R
R
Heinemann
U
U
Elger
C E
CE
D000328:Adult; D001464:Barium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D013111:Spider Venoms / Q000494:pharmacology; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D001464:Barium; D020866:omega-Conotoxin GVIA; D009543:Nifedipine