While our results do not directly address the question of the causative microdomains in the membrane, one obvious candidate is the lipid raft, a cholesterol- and sphingomyelin-rich microdomain in the plasma membrane. We show that cholesterol depletion results in a significant reduction in the development of AFT. Mammalian SLO-1/BK function is known to be modulated by the cholesterol environment in which it resides in the membrane [14], [25]–[27], and the mammalian BK channel is found in lipid rafts [31]. Recent studies suggest that the modulation of channel function by cholesterol is through a specific interaction with a protein surface on the SLO-1/BK channel itself rather than a secondary effect of cholesterol’s effect on lipid packing [25], [27].
