Voltage-dependent Ca2+ currents in epilepsy.
Voltage-dependent Ca2+ channels (VCCs) represent one of the main routes of Ca2+ entry into neuronal cells. Changes in intracellular Ca2+ dynamics and homeostasis can cause long-lasting cellular changes via activation of different Ca2+ dependent signalling pathways. We have investigated the properties of VCCs in human hippocampal dentate granule cells (DGCs) using the whole-cell configuration of the patch-clamp method. Classical high-threshold Ca2+ currents were composed mainly of omega-CgTx-sensitive N-type and nifedipine-sensitive L-type currents that were present in similar proportions. In addition, a Ca2+ current component that was sensitive to low concentrations of Ni2+, but not to nifedipine or omega-conotoxin GVIA (omega-CgTx GVIA) was present. This latter component showed a half-maximal inactivation at more hyperpolarized potentials than high-threshold currents and a more rapid time-dependent inactivation. This current was termed T-type Ca2+ current. Current components with similar pharmacological and kinetic characteristics could be elicited in acutely isolated control rat DGCs. The current density of high threshold and T-type Ca2+ components was significantly larger in human DGCs and in the kainate model compared to DGCs isolated from adult control rats. These differences in current density were not accompanied by parallel differences in the voltage-dependence of VCCs. Taken together, these data suggest that an up-regulation of Ca2+ current density may occur in hippocampal epileptogenesis without consistent changes in Ca2+ current properties.
Department of Experimental Epileptology, University of Bonn Medical Center, Germany. heinz@mailer.meb.uni-bonn.de
H
H
Beck
R
R
Steffens
C E
CE
Elger
U
U
Heinemann
D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D020746:Calcium Channels, L-Type; D018891:Dentate Gyrus / Q000502:physiology / Q000503:physiopathology* / Q000601:surgery; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology* / Q000601:surgery; D006624:Hippocampus / Q000601:surgery; D006801:Humans; D007608:Kainic Acid; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D009474:Neurons / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D010455:Peptides; D020866:omega-Conotoxin GVIA; D009543:Nifedipine; D007608:Kainic Acid