Sodium currents in isolated rat CA1 neurons after kindling epileptogenesis.
Cellular excitability of CA1 neurons from a kindled focus in the rat hippocampus is persistently increased. The changes in the underlying voltage-dependent sodium current were characterized under whole-cell voltage-clamp conditions. We compared sodium currents in acutely isolated CA1 neurons from kindled rats with those in matched controls, one day and five weeks after cessation of kindling stimulations. The sodium current in CA1 neurons was tetrodotoxin sensitive and inactivated completely with two time-constants. In 97 cells from control rats, the current evoked at -20 mV consisted of a fast-inactivating component of 3.8 +/- 0.2 nA which decayed with a time-constant of 1.0 +/- 0.1 ms, and a slow-inactivating component of 1.2 +/- 0.1 nA with a time-constant of 3.6 +/- 0.1 ms. The potential of half-maximal inactivation was -72.2 +/- 1.0 mV for the fast-inactivating component and -63.2 +/- 1.0 mV for the slow-inactivating component. The time-constant of recovery at -80 mV was 14.1 +/- 0.4 ms for the fast-inactivating component and 9.3 +/- 0.4 ms for the slow-inactivating component. One day after kindling, the voltage dependence of inactivation of the slow-inactivating and the fast-inactivating component was shifted in the depolarizing direction (3.2 +/- 1.3 and 3.0 +/- 1.3 mV, respectively). The voltage dependence of recovery from inactivation was shifted in the same direction. Five weeks after kindling, the shift in voltage dependence of inactivation was (3.3 +/- 1.2 and 2.9 +/- 1.2 mV, respectively) and was accompanied by a 20% increase in sodium current amplitude. The voltage-dependent activation was not different after kindling. The changes in sodium current inactivation will increase the number of channels available for activation and may enhance the maximum firing rate. This implies that the changes in sodium current inactivation will contribute to the enhanced excitability of pyramidal neurons observed after kindling.
Vreugdenhil
M
M
Institute for Neurobiology, University of Amsterdam, The Netherlands.
Faas
G C
GC
Wadman
W J
WJ
D000818:Animals; D004827:Epilepsy / Q000503:physiopathology*; D006624:Hippocampus / Q000502:physiology / Q000503:physiopathology*; D007696:Kindling, Neurologic / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D015222:Sodium Channels; D013779:Tetrodotoxin