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

Abstract

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 Ca(2+)-independent channel. The function of the second, large-conductance Ca(2+)-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 x 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+ antagonist 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 = infinity is 279 +/- 8 pS, n = 88) re 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.

Sodium Channels in Transient Retinal Bipolar Cells Enhance Visual Responses in Ganglion Cells

“…The cholinesensitive inward current was smaller than the TTX-sensitive inward current. This may be attributed to the high concentrations of extracellular choline that have been reported to reduce voltage-gated potassium currents (Fatt and Katz, 1953;Schlatter et al, 1993;Delmas and Gola, 1995), which would cause an underestimation of the net inward current. Although the inward current was small, the choline substitution experiment is consistent with the notion that sodium currents exist in a subset of ON bipolar cells that enhance light-evoked voltage responses.…”

Cell-specific regulation of L-WNK1 by dietary K+

“…High tubular flow rates, the consumption of diets with high-K ϩ content, and elevated aldosterone levels stimulate K ϩ secretion in the ASDN (16,24,38,53,73). K ϩ secretion within this segment is mediated by two distinct K ϩ -permeable channels: 1) renal outer medullary K ϩ channel (ROMK), a low-conductance ATP-sensitive K ϩ channel (4,19,21,25,30,76,94,103,107), and 2) BK, a high-conductance K ϩ channel that is activated by membrane depolarization, increases in intracellular Ca 2ϩ concentration, hypoosmotic stress, and membrane stretch (19,20,34,44,62,63,77,79,82,83,87). BK channels are formed by poreforming ␣-subunits and, in most cells, regulatory ␤-subunits (2,14,40,50).…”

Inhibition of MAPK stimulates the Ca 2+ -dependent big-conductance K channels in cortical collecting duct

“…Patch-clamp studies and molecular cloning have demonstrated that ROMK-like small-conductance K (SK) channels (2-4) and big-conductance K (BK) channels (5)(6)(7)(8) are the two main types of K channels in the apical membrane of the cortical collecting duct (CCD). It is generally accepted that ROMK channels are responsible for K secretion under conditions of normal K intake because these channels have high open probability and expression (9).…”