Ca2+ entry through L-type Ca2+ channels helps terminate epileptiform activity by activation of a Ca2+ dependent afterhyperpolarisation in hippocampal CA3

In CA3 neurons of disinhibited hippocampal slice cultures the slow afterhyperpolarisation, following spontaneous epileptiform burst events, was confirmed to be Ca2+ dependent and mediated bp K+ ions. Apamin, a selective blocker of the SK channels responsible for part of the slow afterhyperpolarisation reduced, but did not abolish, the amplitude of the post-burst afterhyperpolarisation. The result was an increased excitability of individual CA3 cells and the whole CA3 network, as measured by burst duration and burst frequency. Increases in excitability could also be achieved by strongly buffering intracellular Ca2+ or by minimising Ca2+ influx into the cell, specifically through L-type (but not N-type) voltage operated Ca2+ channels. Notably the L-type Ca2+ channel antagonist, nifedipine, was more effective than apamin at reducing the post-burst afterhyperpolarisation. Nifedipine also caused a greater increase in network excitability as determined from measurements of burst duration and frequency from whole cell and extracellular recordings. N-methyl D-aspartate receptor activation contributed to the depolarisations associated with the epileptiform activity but Ca2+ entry via this route did not contribute to the activation of the post-burst afterhyperpolarisation. We suggest that Ca2+ entry through L-type channels during an epileptiform event is selectively coupled to both apamin-sensitive and -insensitive Ca2+. activated K+ channels. Our findings have implications for how the route of Ca2+ entry and subsequent Ca2+ dynamics can influence network excitability during epileptiform discharges. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.