ELECTROPHYSIOLOGICAL CHARACTERIZATION OF NA+ CURRENTS IN ACUTELY ISOLATED HUMAN HIPPOCAMPAL DENTATE GRANULE CELLS

1. Properties of voltage-dependent Naf currents were investigated in f orty-two dentate granule cells (DGCs) acutely isolated from the resect ed hippocampus of twenty patients with therapy-refractory temporal lob e epilepsy (TLE) using the whole-cell patch-clamp technique. 2. Depola rizing voltage commands elicited large, rapidly activating and inactiv ating Na+ currents (140 pS mu m(-2); 163 mM extracellular Na+) that we re reduced in amplitude by lowering the Na+ gradient (43 mM extracellu lar Na+). At low temperatures (8-12 degrees 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, resp ectively. In order to reduce series resistance errors, the Na+ current was partially blocked by low toxin concentrations (10-15 nM) in the e xperiments described below. Under these conditions, Na+ currents showe d 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 w ith a double-exponential function (time constants, 3-20 and 60-200 ms) . The rapid and slow time constants showed a distinct voltage dependen ce with maximal values around -55 and -80 mV, respectively. These prop erties contributed to a reduction of the Na+ currents during repetitiv e stimulation that was more pronounced with higher stimulation frequen cies and also showed a dependence on the holding potential. 5. In summ ary, the most striking features of DGC Naf currents were the large cur rent density and the presence of a current component showing a slow re covery from inactivation. Our data provide a basis for comparision wit h properties of Na+ currents in animal models of epilepsy, and for the study of drug actions in therapy-refractory epilepsy.