Physiological importance of SK2 in whole body K+ homeostasis. (360G-Wellcome-083175_Z_07_Z)

Regulated K+ secretion by the renal collecting duct is critical for regulation of whole body K+ homeostasis. Although the K+ channel ROMK plays an important role in this process, it is clear that additional K+ channels are also involved, e.g. BK channels in response to changes in tubular flow and dietary K+. Previous and preliminary work suggests that SK2 also plays a role in this process. In preliminary experiments plasma K+ in SK2 KO mice was increased and the fractional excretion of K+ was reduced, consistent with a role for SK2 in K+ secretion. The aim of the proposed project is to examine this further, using in vivo, molecular, fluorescence and electrophysiological approaches. Experiments will compare wildtype and SK2 KO mice examining whole renal function under control, volume expanded conditions and in response to changes in dietary K+. Molecular and fluorescence approaches will determine the cellular location of SK2. These experiments will also examine whether different K+ diets alter SK2 expression. Finally, electrophysiological studies will be used to identify SK2 at a functional level and examine physiological regulation. Elucidating the mechanisms underlying renal K+ secretion will increase our understanding of renal physiology in both health and disease.