Flow-dependent K+ secretion in the cortical collecting duct is mediated by a maxi-K channel.
K+ secretion by the cortical collecting duct (CCD) is stimulated at high flow rates. Patch-clamp analysis has identified a small-conductance secretory K+ (SK) and a high-conductance Ca(2+)-activated K+ (maxi-K) channel in the apical membrane of the CCD. The SK channel, encoded by ROMK, is believed to mediate baseline K+ secretion. The role of the stretch- and Ca2+-activated maxi-K channel is still uncertain. The purpose of this study was to identify the K+ channel mediating flow-dependent K+ secretion in the CCD. Segments isolated from New Zealand White rabbits were microperfused in the absence and presence of luminal tetraethylammonium (TEA) or charybdotoxin, both inhibitors of maxi-K but not SK channels, or apamin, an inhibitor of small-conductance maxi-K+ channels. Net K+ secretion and Na+ absorption were measured at varying flow rates. In the absence of TEA, net K+ secretion increased from 8.3 +/- 1.0 to 23.4 +/- 4.7 pmol. min(-1). mm(-1) (P < 0.03) as the tubular flow rate was increased from 0.5 to 6 nl. min(-1). mm(-1). Flow stimulation of net K+ secretion was blocked by luminal TEA (8.2 +/- 1.2 vs. 9.9 +/- 2.7 pmol. min(-1). mm(-1) at 0.6 and 6 nl. min(-1). mm(-1) flow rates, respectively) or charybdotoxin (6.8 +/- 1.6 vs. 8.3 +/- 1.6 pmol. min(-1). mm(-1) at 1 and 4 nl. min(-1). mm(-1) flow rates, respectively) but not by apamin. These results suggest that flow-dependent K+ secretion is mediated by a maxi-K channel, whereas baseline K+ secretion occurs through a TEA- and charybdotoxin-insensitive SK (ROMK) channel.
Woda
C B
CB
Division of Pediatric Nephrology, Department of Pediatrics, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6574, USA.
Bragin
A
A
Kleyman
T R
TR
Satlin
L M
LM
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D015153:Blotting, Western; D018999:Charybdotoxin / Q000494:pharmacology; D005260:Female; D005455:Fluorescent Antibody Technique; D007672:Kidney Cortex / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008465:Mechanoreceptors / Q000502:physiology; D008856:Microscopy, Fluorescence; D009399:Nephrons / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated; D011817:Rabbits; D051640:Small-Conductance Calcium-Activated Potassium Channels; D019789:Tetraethylammonium / Q000494:pharmacology
D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D018999:Charybdotoxin; D001030:Apamin; D019789:Tetraethylammonium; D011188:Potassium