Renal fluid and electrolyte handling in BKCa-beta1-/- mice

Large-conductance Ca2+-activated K+ channels (BKCa) are composed of pore-forming -subunits and one of four accessory -subunits. The 1-subunit, found predominantly in smooth muscle, modulates the Ca2+ sensitivity and pharmacological properties of BKCa. BKCa-1 null mice (M1/) are moderately hypertensive, consistent with the role of BKCa in modulating intrinsic vascular tone. Because BKCa are present in various renal cells including the mesangium and cortical collecting ducts, we determined whether fluid or electrolyte excretion was impaired in M1/ under euvolemic, volume-expanded, or high-salt diet conditions. Under euvolemic conditions, no differences in renal function were found between M1/ and M1+/+. However, glomerular filtration rate (GFR) and fractional K+ excretion were significantly impaired in M1/ in response to acute volume expansion. In contrast, M1/ exhibited enhanced Na+ excretion and fractional Na+ excretion responses to acute volume expansion. Differences in renal function between M1+/+ and M1/ were not observed when chronically treated with a high-salt diet. These observations indicate that the 1-subunit of BKCa 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.