M current is one of the major mechanisms controlling the neuronal excitability.Its regulation is represented by two G protein coupled receptor pathways, M type acetylcholine receptor (M1) and type Ⅱ bradykinin receptor (B2).However, the underlying mechanisms are different, with key difference in the effects on intracellular Ca2+ concentration.Recent studies have reported that lipid rafts play important roles in cell signaling transduction; the signaling molecules concentrated in the lipid raft might determine the specificity of various cell signaling.This study is intended to understand the mechanism of M current modulation by different ceil signaling pathways from the point of lipid raft.We found that the sucrose density gradient yielded the best resolution of caveolin-1 in raft fractions in rat SCG neurons.B2R and other related signaling moleculars were found in raft fraction.As for M1 receptor, there was little localization in lipid raft fractions.Amphotericin B-perforated patch recording demonstrated that the inhibition of M current induced by BK was significantly reduced after 5 mM MβCD application, but not for OXO-M.Futhermore, BK-induced intracellular Ca2+ rising could also be greatly reduced on the conditioning of MβCD treatment.We also found that in SCG neurons, caveolin-1 seemed to have more co-localization with B2R than with M1R.All together, lipid rafts play an important role in BK mediated inhibition of M currents in SCG neurons.