Cation specificity and pharmacological properties of the Ca2+-dependent K+ channel of rat cortical collecting ducts

The luminal membrane of principal cells of rat cortical collecting duct (CCD) is dominated by a K+ conductance. Two different K+ channels are described for this membrane. K+ secretion probably occurs via a small-conductance Ca2+-independent channel. The function of the second, large-conductance Ca2+-dependent channel is unclear. This study examines properties of this channel to allow a comparison of this K+ channel with the macroscopic K+ conductance of the CCD and with similar K+ channels from other preparations. The channel is poorly active on the cell. It has a conductance of 263±11 pS (n=36, symmetrical K+ concentrations) and of 139±3 pS (n=91) with 145 mmol/l K+ on one side and 3.6 mmol/l K+ on the other side of the membrane. Its open probability is high after excision (0.71±0.03, n=85). The channel flickers rapidly between open and closed states. Its permeability in the cell-free configuration was 7.0±0.2×10−13 cm3/s (n=85). It is inhibited by several typical blockers of K+ channels such as Ba2+, tetraethylammonium, quinine, and quinidine and high concentrations of Mg2+. The Ca2+ antagonists verapamil and diltiazem also inhibit this K+ channel. As is typical for the maxi K+ channel, it is inhibited by charybdotoxin but not by apamin. The selectivity of this large-conductance K+ channel demonstrates significant differences between the permeability sequence (PK > PRb > PNH4 > PCs=PLi=PNa=Pcholine=0) and the conductance sequence (gK > gNH4 > gRb > gLi=gcholine > gCs=gNa=0). The only other cations that are significantly conducted by this channel besides K+ (gK at Vc =∞ is 279±8 pS, n=88) are NH 4 + (gNH4=127±22 pS, n=10) and Rb+ (gRb=36±5 pS, n=6). The K+ currents through this channel are reduced by high concentrations of choline+, Cs+, Rb+, and NH 4 + . These properties and the dependence of this channel on Ca2+ and voltage classify it as a “maxi” K+ channel. A possible physiological function of this channel is discussed in the accompanying paper.