NiCl2 and amiloride induce spreading depression in guinea pig hippocampal slices

Spreading depressions (SD) occur in association with ischaemia, epilepsy an d migraine. Intracellular calcium oscillations have been suggested to be in volved in the generation and propagation of SD. The present study was perfo rmed to study the mechanism of conditioning guinea pig hippocampal slices b y the T-type calcium channel blockers NiCl2 and amiloride. SD-like fluctuat ions of DC potential were recorded by inserting microelectrodes into the CA 1 and CA3 regions. The SD occurrence was significantly greater with 10 mu m ol/l NiCl2 as well as with 25 and 50 mu mol/l amiloride than with other con centrations of these substances. The concentration response curve was inver sely U-shaped with the maximum repetition rates of SDs being achieved at 10 mu mol/l NiCl2 as well as at 25 and 50 mu mol/l amiloride. SD occurrence c ould be completely blocked by the NMDA antagonist APV (10 mu mol/l) in all cases. These data demonstrate that modulation of the Ca2+ dynamics conditio ned guinea pig hippocampal slices and increased their susceptibility to gen erate SD.