Renal fluid and electrolyte handling in BK_Ca-β1^-/- mice

Large-conductance Ca²⁺-activated K⁺ channels (BK_Ca) are composed of pore-forming α-subunits and one of four accessory β-subunits. The β1subunit, found predominantly in smooth muscle, modulates the Ca²⁺ sensitivity and pharmacological properties of BK_Ca. BK_Ca-β1 null mice (Mβ1^-/-) are moderately hypertensive, consistent with the role of BK_Ca in modulating intrinsic vascular tone. Because BK_Ca are present in various renal cells including the mesangium and cortical collecting ducts, we determined whether fluid or electrolyte excretion was impaired in Mβ1^-/- under euvolemic, volume-expanded, or high-salt diet conditions. Under euvolemic conditions, no differences in renal function were found between Mβ1^-/- and Mβ1^+/+. However, glomerular filtration rate (GFR) and fractional K⁺ excretion were significantly impaired in Mβ1^-/- in response to acute volume expansion. In contrast, Mβ1^-/- exhibited enhanced Na⁺ excretion and fractional Na⁺ excretion responses to acute volume expansion. Differences in renal function between Mβ1^+/+ and Mβ1^-/- were not observed when chronically treated with a high-salt diet. These observations indicate that the β1-subunit of BK_Ca contributes to the increased GFR that accompanies an acute salt and volume load and raises the possibility that it is also involved in regulating K⁺ excretion under these conditions.