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 hippocampus induces a persistent epileptogenic focus in area CA1. Neurons were enzymatically isolated from the focal region one day or six weeks after seven class V generalized seizures had been evoked. Calcium currents were measured under voltage-clamp conditions in the whole-cell patch configuration. One day after kindling, as well as six weeks later, the amplitudes of a slow-inactivating (tau = 90 ms) and a non-inactivating calcium current component were, in comparison to controls, enhanced by 30 and 40%, respectively. This enhancement was therefore related to the kindled state of enhanced excitability. The enhancement of the calcium current was independent of the steady-state intracellular calcium concentration. Fast calcium-dependent inactivation was provoked with double-pulse protocols that conditioned the neuron with a defined calcium-influx in the first pulse. Despite the larger calcium current during the conditioning pulse, the relative calcium-dependent inactivation of the sustained current component was reduced in neurons from the kindled focus. Repetitive depolarizations, once every second, evoked a cumulative calcium-dependent inactivation. Nothwithstanding the larger calcium current, kindling also persistently reduced this slow inactivation of both transient and sustained high threshold calcium current. The reduction in calcium-dependent inactivation cannot be responsible for the increased current, but can certainly enhance the calcium influx during prolonged activation or seizures. The changes can be explained by assuming that additional calcium channels are recruited at a location that prevents calcium-dependent inactivation.
Vreugdenhil
M
M
Department of Experimental Zoology, University of Amsterdam, The Netherlands.
Wadman
W J
WJ
D000818:Animals; D002118:Calcium / Q000502:physiology*; D004553:Electric Conductivity; D006624:Hippocampus / Q000503:physiopathology*; D007696:Kindling, Neurologic; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D002118:Calcium