Properties of Voltage-Activated Ca2+ Currents in Acutely Isolated Human Hippocampal Granule Cells

Abstract

Beck, H., R. Steffens, U. Heinemann, and C. E. Elger. Properties of voltage-activated Ca2+ currents in acutely isolated human hippocampal granule cells. J. Neurophysiol. 77: 1526–1537, 1997. Properties of Ba2+ currents through voltage-dependent Ca2+ channels ( I Ba) 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 ( V 1/2inact) of −16.4 mV. Application of saturating doses of ω-conotoxin (ω-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 ω-agatoxin IVA (ω-AgaTx IVA)-sensitive but ω-CgTx MVIIC-insensitive, noninactivating component of HVA currents (∼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( V 1/2inact = −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 ω-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.