The apical 70-pS K+ channel in the thick ascending limb of Henle's loop is a large-conductance Na+-and Cl--activated, KNa1.1-like, channel

Apical K+ channels are crucial for the thick ascending limb (TAL) of Henle's loop transport function. The renal outer medullary K+ (ROMK) channel gene (KNCJ1) encodes a 30-pS K+ channel whose loss of function causes reduced NaCl reabsorption in the TAL associated with type 2 Bartter's syndrome. In contrast, the molecular basis of a functionally ROMK-related 70-pS K+ channel is still unclear. The aim of this study was to highlight new specific channel properties that may give insights into its molecular identity. Using the patch-clamp technique on the apical membrane of mouse split-open TAL tubules, we observed that 70-pS K+ channel activity, but not ROMK channel activity, increases with internal Na+ and Cl- concentrations, with relative 50% effective concentrations (EC50) and Hill coefficients (n(H)) of 40.6 mM (SD 1.65) and 2.4 (SD 0.28) for Na+ and of 29.3 mM (SD 2.35) and 2.2 (SD 0.39) for Cl-. Conversely, 70-pS K+ channel activity was inhibited by internal K+ with a relative EC50 of 64 mM (SD 13.5) and n(H) of 3.5 (SD 2.3) and by internal NH4+ and Ca2+. The reevaluation of channel conductive properties revealed an actual inward conductance of similar to 170 pS, with multiple subconductance levels, an inward rectification, and a substantial permeability to NH4+ (P-NH4/P-K = 0.2). We conclude that the apical 70-pS K+ channel in TAL cells is a large-conductance Na+- and Cl--activated K+ channel functionally resembling a K(Na)1.1 channel and propose that ROMK determines its functional expression possibly at the level of channel protein synthesis or trafficking.