Electrophysiological characterization of Na+ currents in acutely isolated human hippocampal dentate granule cells.
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 microm-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.
Reckziegel
G
G
Department of Epileptology, University of Bonn Medical Center, D-53105 Bonn, Germany. umc805@ibm.rhrz.uni-bonn.de
Beck
H
H
Schramm
J
J
Elger
C E
CE
Urban
B W
BW
D000328:Adult; D000465:Algorithms; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D004594:Electrophysiology; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008839:Microelectrodes; D018408:Patch-Clamp Techniques; D012530:Saxitoxin / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D015222:Sodium Channels; D012530:Saxitoxin; D013779:Tetrodotoxin