PROPERTIES OF VOLTAGE-ACTIVATED CA2+ CURRENTS IN ACUTELY ISOLATED HUMAN HIPPOCAMPAL GRANULE CELLS

Properties of Ba2+ currents through voltage-dependent Ca2+ channels (I -Ba) were investigated in 61 dentate granule cells acutely isolated fr om the resected hippocampus of nine patients with therapy-refractory t emporal lobe epilepsy (TLE). Currents with a high threshold of activat ion (HVA) peaked at 0 mV, and showed some time-dependent inactivation and a voltage of half-maximal steady-state inactivation (V-1/2inact) o f -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 b oth agents blocked HVA currents by >95%. In a 10-mo-old child but not in adult patients, an omega-agatoxin IVA (omega-AgaTx IVA)-sensitive b ut omega-CgTx MVIIC-insensitive, noninactivating component of HVA curr ents (similar to 24%) was present that most probably corresponds to a P-type current. A T-type Ca2+ current could be separated from HVA comp onents on the basis of its steady-state voltage-dependent inactivation (V-1/2inact = -71.0 mV). The T-type Ca2+ current isolated by subtract ion peaked at more negative potentials (-10 mV), showed a significantl y more rapid time-dependent inactivation, and could be selectively blo cked by low concentrations of Ni2+. It was insensitive to nifedipine a nd omega-CgTx GVIA. We conclude that L-, N-, and T-type currents are p resent in adult human dentate granule cells and an additional P-type c urrent 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 h uman disease.