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THE interaction between the Ca2+-activated K+ currents (IK(Ca)) induced by acetylcholine (ACh), 1-aminocyclopentane-1S,3R-dicarboxylic acid ((1S,3R)-ACPD) and caffeine in rat hippocampal CA1 neurones was investigated to examine the functional independence between IP3- and Ca2+-sensitive Ca2+ stores. Pretreatment with either ACh or (1S,3R)-ACPD almost completely suppressed the subsequent IK(Ca) induced by another. Pretreatment with caffeine partially suppressed the IK(Ca) induced by either ACh or (1S,3R)-ACPD, although the inhibitory effect varied among the neurones, while pretreatment with either ACh or (1S,3R)-ACPD also partially inhibited the caffeine-induced IK(Ca). Continuous treatment with ryanodine and thapsigargin non- selectively decreased both the caffeine- and ACh-induced IK(Ca). These results thus indicate a close interaction between IP3- and Ca2+-sensitive stores and also suggest that the relative size of both stores and the closeness between them differ among neurones.