Ca2+ entry through L-type Ca2+ channels helps terminate epileptiform activity by activation of a Ca2+ dependent afterhyperpolarisation in hippocampalCA3

In CA3 neurons of disinhibited hippocampal slice cultures the slow afterhyp erpolarisation, following spontaneous epileptiform burst events, was confir med to be Ca2+ dependent and mediated bp K+ ions. Apamin, a selective block er of the SK channels responsible for part of the slow afterhyperpolarisati on reduced, but did not abolish, the amplitude of the post-burst afterhyper polarisation. The result was an increased excitability of individual CA3 ce lls and the whole CA3 network, as measured by burst duration and burst freq uency. Increases in excitability could also be achieved by strongly bufferi ng intracellular Ca2+ or by minimising Ca2+ influx into the cell, specifica lly through L-type (but not N-type) voltage operated Ca2+ channels. Notably the L-type Ca2+ channel antagonist, nifedipine, was more effective than ap amin at reducing the post-burst afterhyperpolarisation. Nifedipine also cau sed a greater increase in network excitability as determined from measureme nts of burst duration and frequency from whole cell and extracellular recor dings. N-methyl D-aspartate receptor activation contributed to the depolari sations associated with the epileptiform activity but Ca2+ entry via this r oute did not contribute to the activation of the post-burst afterhyperpolar isation. We suggest that Ca2+ entry through L-type channels during an epileptiform e vent 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 Scien ce Ltd. All rights reserved.