Properties of a Delayed Rectifier Potassium Current in Dentate Granule Cells Isolated from the Hippocampus of Patients with Chronic Temporal Lobe Epilepsy

Abstract
Summary: Purpose: Properties of potassium outward currents were investigated in human hippocampal dentate gyrus granule cells from 11 hippocampal specimens obtained from patients with temporal lobe epilepsy (TLE) during resective surgery. Methods: Dentate granule cells were isolated enzymatically and outward currents analyzed by using the whole‐cell configuration of the patch‐clamp method. Hippocampal specimens were classified neuropathologically with respect to severe segmental cell loss, gliosis, and axonal sprouting (Ammon's horn sclerosis, AHS), or the presence of a focal lesion in the adjacent temporal lobe. Results: A delayed rectifier outward current (I), but not an A‐type potassium current (Ik) or inwardly rectifying potassium currents, was observed in all cells. The average current density of Ik, the time‐dependent decay of Ik, and the resting membrane characteristics were not significantly different between patients with and without AHS. The voltage of half‐maximal activation V1/2(act) was 5·4 ± 1·8 mV in AHS compared with −2·9 ± 1·8 mV in lesion‐associated epilepsy (NS). In contrast, V1/2(inact) was shifted in a hyperpolarizing direction in AHS (−67·7 ± 0·6 mV) compared with that in hippocampi not showing AHS (−47·7 ± 2·6 mV; p = 0·0017). Conclusions: The altered steady‐state voltage‐dependence of Ik, may result in abnormal excitability of dentate granule cells in AHS and exert a marked influence on input‐output properties of the dentate gyrus.