Using inside-out configuration of patch clamp techniques, ATP modulation of BKca channels was studied in hippocampal CAI pyramidal neurons of adult rat. Intracellular ATP application markedly increased BKca channel activity, and this ATP-produced increase in BK, channel activity was characterized by a higher opening frequency with no changes in channel open times. In the presence of specific inhibitor against protein kinase A, H-89, ATP did not induce any increase in the channel activity. Furthermore, adding H-89 after addition of ATP reversed the modulation produced by ATE In contrast, protein kinase C inhibitor chelerythrine exerted no apparent effects on ATP-induced channel activation. The present study suggests that BKca channels from hippocampal CA1 pyramidal neurons could be modulated by ATP via a functionally associated orotein kinase A-like orotein.