Electrophysiological characterization of Na+ currents in acutely isolated human hippocampal dentate granule cells

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Abstract
1 Properties of voltage‐dependent Na+ currents were investigated in forty‐two dentate granule cells (DGCs) acutely isolated from the resected hippocampus of twenty patients with therapy‐refractory temporal lobe epilepsy (TLE) using the whole‐cell patch‐clamp technique. 2 Depolarizing voltage commands elicited large, rapidly activating and inactivating Na+ currents (140 pS μm−2; 163 mm extracellular Na+) that were reduced in amplitude by lowering the Na+ gradient (43 mm extracellular Na+). At low temperatures (8‐12 °C), the time course of Na+ currents slowed and could be well described by the model of Hodgkin & Huxley. 3 Na+ currents were reversibly blocked by tetrodotoxin (TTX) and saxitoxin (STX) with a half‐maximal block of 4.7 and 2.6 nm, respectively. In order to reduce series resistance errors, the Na+ current was partially blocked by low toxin concentrations (10‐15 nm) in the experiments described below. Under these conditions, Na+ currents showed a threshold of activation of about ‐50 mV, and the voltages of half‐maximal activation and inactivation were ‐29 and ‐55 mV, respectively. 4 The time course of recovery from inactivation could be described with a double‐exponential function (time constants, 3‐20 and 60‐200 ms). The rapid and slow time constants showed a distinct voltage dependence with maximal values around ‐55 and ‐80 mV, respectively. These properties contributed to a reduction of the Na+ currents during repetitive stimulation that was more pronounced with higher stimulation frequencies and also showed a dependence on the holding potential. 5 In summary, the most striking features of DGC Na+ currents were the large current density and the presence of a current component showing a slow recovery from inactivation. Our data provide a basis for comparison with properties of Na+ currents in animal models of epilepsy, and for the study of drug actions in therapy‐refractory epilepsy.