Cholesterol inhibits constitutively open inwardly-rectifying potassium channels25, 26 but appears to activate cardiac (GIRK1/GIRK4) and brain (GIRK2) channels23, 27, 43. Whether cholesterol acts directly on brain GIRK2 channels in the absence of Gβγ is unknown. Using GIRK2-containing liposomes that have brain PIP2 (1%), we examined the effect of cholesterol on the relative K+ flux. The basal rate of K+ flux through GIRK2 channels was significantly enhanced in membranes containing 5% cholesterol (Fig. 4a). Both 5% and 10% cholesterol significantly increased the relative rate of K+ flux, while 1% was ineffective (Fig. 4b ). Interestingly, the relative rate of K+ flux was similar for 5% and 10% cholesterol, suggesting near saturation for this response.
