Screening assays for identifying agents that modulate BK channel activity and further modulate the sleep/wake cycle in a subject, circadian regulated locomotor activity in a subject, or both are provided, as are agents identified using such screening assays. Also provided are methods of modulating the sleep/wake cycle in a subject and methods of modulating circadian regulated locomotor activity in a subject by administering an agent that modulates BK channel activity to the subject, for example, an agent identified by a screening assay as disclosed.