Renal fluid and electrolyte handling in BK Ca -β1 −/− mice

Large-conductance Ca 2+ -activated K + channels (BK Ca ) are composed of pore-forming α-subunits and one of four accessory β-subunits. The β1-subunit, found predominantly in smooth muscle, modulates the Ca 2+ 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.