NiCl2 and amiloride induce spreading depression in guinea pig hippocampal slices

Spreading depressions (SD) occur in association with ischaemia, epilepsy and migraine. Intracellular calcium oscillations have been suggested to be involved in the generation and propagation of SD. The present study was performed to study the mechanism of conditioning guinea pig hippocampal slices by the T-type calcium channel blockers NiCl2 and amiloride. SD-like fluctuations of DC potential were recorded by inserting microelectrodes into the CA1 and CA3 regions. The SD occurrence was significantly greater with 10 mu mol/l NiCl2 as well as with 25 and 50 mu mol/l amiloride than with other concentrations of these substances. The concentration response curve was inversely 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 could be completely blocked by the NMDA antagonist APV (10 mu mol/l) in all cases. These data demonstrate that modulation of the Ca2+ dynamics conditioned guinea pig hippocampal slices and increased their susceptibility to generate SD.