Nitric oxide directly activates large conductance Ca2+-activated K+ channels (rSlo)

We investigated whether nitric oxide (NO) directly activates the cloned a-s ubunit of large conductance Ca2+-activated K+ (Maxi-K) channels from rat br ain (rSlo), expressed either in HEK293 cells or Xenopus oocytes. In inside- out patches, the application of S-nitroso-N-acetylpenicillamine (SNAP), a N O-releasing compound, reversibly activated the channel shifting the voltage dependent activation curve of the macroscopic Maxi-K current to the left b y about 15 mV. Pretreatment of the patches with N-ethylmaleimide to alkylat e free sulfhydryl groups did not prevent the effect of SNAP, suggesting tha t NO may directly interact with the channels. These results suggest that Ma xi-K channels might be one of the physiological targets of NO in the brain.