SODIUM CURRENTS IN ISOLATED RAT CA1 NEURONS AFTER KINDLING EPILEPTOGENESIS

Cellular excitability of CA1 neurons from a kindled focus in the rat h ippocampus is persistently increased. The changes in the underlying vo ltage-dependent sodium current were characterized under whole-cell vol tage-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 c urrent in CA1 neurons was tetrodotoxin sensitive and inactivated compl etely with two time-constants. In 97 cells from control rats, the curr ent 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 lime-constant o f 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 f or 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 direct ion (3.2 +/- 1.3 and 3.0 +/- 1.3 mV, respectively). The Voltage depend ence of recovery from inactivation was shifted in the same direction. Five weeks after kindling, the shift in voltage dependence of inactiva tion was (3.3 +/- 1.2 and 2.9 +/- 1.2 mV, respectively) and was accomp anied by a 20% increase in sodium current amplitude. The voltage-depen dent activation was not different after kindling. The changes in sodiu m current inactivation will increase the number of channels available for activation and may enhance the maximum firing rate. This implies t hat the changes in sodium current inactivation will contribute to the enhanced excitability of pyramidal neurons observed after kindling. (C ) 1998 IBRO. Published by Elsevier Science Ltd.