VOLTAGE-DEPENDENT CA2+ CURRENTS IN EPILEPSY

Voltage-dependent Ca2+ channels (VCCs) represent one of the main route s of Ca2+ entry into neuronal cells. Changes in intracellular Ca2+ dyn amics and homeostasis can cause long-lasting cellular changes via acti vation of different Ca2+ dependent signalling pathways. We have invest igated the properties of VCCs in human hippocampal dentate granule cel ls (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 w ere present in similar proportions. In addition, a Ca2+ current compon ent that was sensitive to low concentrations of Ni2+, but not to nifed ipine or omega-conotoxin GVIA (omega-CgTx GVIA) was present. This latt er component showed a half-maximal inactivation at more hyperpolarized potentials than high-threshold currents and a more rapid time-depende nt inactivation. This current was termed T-type Ca2+ current. Current components with similar pharmacological and kinetic characteristics co uld be elicited in acutely isolated control rat DGCs. The current dens ity of high threshold and T-type Ca2+ components was significantly lar ger in human DGCs and in the kainate model compared to DGCs isolated f rom 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+ curr ent density may occur in hippocampal epileptogenesis without consisten t changes in Ca2+ current properties. (C) 1998 Elsevier Science B.V. A ll rights reserved.