G. Reckziegel et al., ELECTROPHYSIOLOGICAL CHARACTERIZATION OF NA+ CURRENTS IN ACUTELY ISOLATED HUMAN HIPPOCAMPAL DENTATE GRANULE CELLS, Journal of physiology, 509(1), 1998, pp. 139-150
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.