The Journal of Neurophysiology Vol. 77 No. 3 March 1997, pp. 1526-1537
Copyright ©1997 The American Physiological Society

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

H. Beck¹, R. Steffens¹, U. Heinemann², and C. E. Elger¹

¹ Department of Epileptology, University of Bonn Medical Center, D-53105 Bonn, Germany; and ² Department of Neurophysiology, Institute of Physiology, Charité Berlin, D-10000 Berlin, Germany

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 -conotoxin (-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 -agatoxin IVA (-AgaTx IVA)-sensitive but -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 -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.

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