Enhancement of calcium currents in rat hippocampal CA1 neurons induced by kindling epileptogenesis.
Kindling of the Schaffer collaterals in the dorsal hippocampus of the rat induced an epileptogenic focus in area CA1. Pyramidal neurons were acutely isolated from this area in fully kindled rats one day after the last class five generalized seizure. Calcium currents were measured in these cells under the whole-cell patch voltage-clamp condition after blockade of sodium and potassium currents. Voltage-dependent calcium currents were activated by depolarizing voltage steps from different prepulse potentials. Calcium currents activated at 0 mV consisted of a sustained component and two voltage-dependent inactivating components. Current inactivation was fitted with two exponentials (time-constants of 13 and 72 ms) and a constant. When cells from kindled rats were compared with those from controls, the amplitudes of the slow-inactivating and the sustained component were significantly enhanced by 36% and 39%, respectively; the fast inactivating current showed only a small enhancement. Inactivation kinetics, time-to-peak and voltage dependency of activation and steady-state inactivation were unchanged. Shape and size of the analysed cells from kindled rats were not different from those in controls. We concluded that an increased specific calcium conductance of as yet unknown origin underlies the larger current. The magnitude of the observed changes is such that it will considerably increase calcium influx and consequently raise intracellular calcium concentration during tetanic stimulation and subsequent periods of paroxysmal activity. This increase will modulate calcium-dependent factors that regulate neuronal excitability and may lead to the enhanced excitability found in kindled tissue.
Vreugdenhil
M
M
Department of Experimental Zoology, University of Amsterdam, The Netherlands.
Wadman
W J
WJ
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D004594:Electrophysiology; D004827:Epilepsy / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007696:Kindling, Neurologic / Q000502:physiology*; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D011712:Pyramidal Tracts / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar
D015220:Calcium Channels