Activity of the basolateral K+ channels is coupled to the Na+-K+-ATPase in the cortical collecting duct.
Microelectrode and patch-clamp techniques were used in the isolated cortical collecting duct to study the effects of stimulating Na+-K+-ATPase by raising bath K+ (Fujii Y and Katz AI. Am J Physiol Renal Fluid Electrolyte Physiol 257: F595-F601, 1989 and Muto S, Asano Y, Seldin D, and Giebisch. Am J Physiol Renal Physiol 276: F143-F158, 1999) on the transepithelial (VT) and basolateral membrane (VB) voltages and basolateral K+ channel activity. Increasing bath K+ from 2.5 to 8.5 mM resulted in an initial hyperpolarization of both VT and VB followed by a delayed depolarization. The effects of raising bath K+ on VT and VB were attenuated by decreasing luminal Na+ from 146.8 to 14.0 mM and were abolished by removal of luminal Na+, whereas those were magnified in desoxycorticosterone acetate (DOCA)-treated rabbits. Increasing bath K+ also led to a significant reduction of the intracellular Na+ and Ca2+ concentrations. The transepithelial conductance (GT) or fractional apical membrane resistance (fRA) were unaltered during the initial hyperpolarization phase, whereas, in the late depolarization phase, there were an increase in GT and a decrease in fRA, both of which were attenuated in the presence of low luminal Na+ (14.0 mM). In tubules from DOCA-treated animals, bath Ba2+ not only caused a significantly larger initial hyperpolarization of VT and VB but also blunted the late depolarization by high bath K+. Nomega-nitro-l-arginine methyl ester (l-NAME) partially mimicked the effect of Ba2+ and decreased the amplitude of the late depolarization. Patch-clamp experiments showed that raising bath K+ from 2.5 to 8.5 mM resulted in an increased activity of the basolateral K+ channel, which was absent in the presence of l-NAME. We conclude that stimulation of Na+-K+-ATPase increases the basolateral K+ conductance and that this effect involves suppression of nitric oxide-dependent inhibition of K+ channels.
Muto
Shigeaki
S
Department of Nephrology, Jichi Medical School, Minamikawachi, Kawachi, Tochigi, 329-0498 Japan. smuto@jichi.ac.jp
Asano
Yasushi
Y
Wang
WenHui
W
Seldin
Donald
D
Giebisch
Gerhard
G
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002462:Cell Membrane / Q000502:physiology; D003900:Desoxycorticosterone / Q000494:pharmacology; D004553:Electric Conductivity; D017097:Electric Impedance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism* / Q000502:physiology; D007672:Kidney Cortex; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D008839:Microelectrodes; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism* / Q000502:physiology; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D004791:Enzyme Inhibitors; D015221:Potassium Channels; D001464:Barium; D003900:Desoxycorticosterone; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester