KINDLING-INDUCED LONG-LASTING ENHANCEMENT OF CALCIUM CURRENT IN HIPPOCAMPAL CA1 AREA OF THE RAT - RELATION TO CALCIUM-DEPENDENT INACTIVATION

Daily tetanization of the Schaffer collaterals (kindling) in the rat h ippocampus induces a persistent epileptogenic focus in area CA1. Neuro ns were enzymatically isolated from the focal region one day or six we eks after seven class V generalized seizures had been evoked. Calcium currents were measured under voltage-clamp conditions in the whole-cel l patch configuration. One day after kindling, as well as six weeks la ter, the amplitudes of a slow-inactivating (tau = 90 ms) and a non-ina ctivating calcium current component were, in comparison to controls, e nhanced by 30 and 40%, respectively. This enhancement was therefore re lated to the kindled state of enhanced excitability. The enhancement o f the calcium current was independent of the steady-state intracellula r calcium concentration. Fast calcium-dependent inactivation was provo ked with double-pulse protocols that conditioned the neuron with a def ined calcium-influx in the first pulse. Despite the larger calcium cur rent during the conditioning pulse, the relative calcium-dependent ina ctivation of the sustained current component was reduced in neurons fr om the kindled focus. Repetitive depolarizations, once every second, e voked a cumulative calcium-dependent inactivation. Nothwithstanding th e larger calcium current, kindling also persistently reduced this slow inactivation of both transient and sustained high threshold calcium c urrent. The reduction in calcium-dependent inactivation cannot be resp onsible for the increased current, but can certainly enhance the calci um influx during prolonged activation or seizures. The changes can be explained by assuming that additional calcium channels are recruited a t a location that prevents calcium-dependent inactivation.