Objective: In the retinal pigment epithelium (RPE) the activation of L-type Ca²⁺ channels regulates different physiologically important cell functions like phagocytosis. Recently a direct coupling of large-conductance voltage- and Ca²⁺-activated K⁺ channel (BK channel) activity to L- type Ca²⁺ channel activation and a negative feedback control of these Ca²⁺ channels have been described (Wimmers et al. 2008, Molecular Vision). Aim of this study was to investigate the relevance of these interactions for phagocytosis. Methods: To analyze the role of BK channels in phagocytosis mice deficient for the pore-forming channel protein of BK channels were used (BK-/-). For in vivo measurement of circadian rhythm of retinal phagocytosis we labeled the outer segment protein rhodopsin in retinal cross-sections of mice and quantified rhodopsin-positiv phagosoms in the RPE at two time points during the day: 30 minutes and 8 hours after onset of light in the morning. Results: In the morning (30 min after onset of light) phagocytic activity showed in the wildtype mice a peak of 11±4 phagosomes/ 100mm retina which decreased to a base level of 4±2 phagosomes/ 100 mm (8h after onset of light). In the BK-/- mice we observed an increase of the peak activity to 15±5 phagosomes / 100mm and a return to lower base level of 2.5±2 phagosomes/ 100mm. Both, the peak phagocytic activity in the morning and during the afternoon were significantly different (P< 0.001). Additionally we observed in the BK-/- mice a decrease in photoreceptor outer segment length, where we measured a ratio outer segment length/ inner segment length of 1.83±0.6 compared with 2.23±0.8 in wildtype mice. Conclusion: In conclusion, the absence of BK channels lead to altered circadian regulation of phagocytic function of the RPE. These data indicate for the first time a role of ion channels in the regulation of phagocytosis by the RPE.