Cytosolic potassium controls CFTR deactivation in human sweat duct.
Absorptive epithelial cells must admit large quantities of salt (NaCl) during the transport process. How these cells avoid swelling to protect functional integrity in the face of massive salt influx is a fundamental, unresolved problem. A special preparation of the human sweat duct provides critical insights into this crucial issue. We now show that negative feedback control of apical salt influx by regulating the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel activity is key to this protection. As part of this control process, we report a new physiological role of K(+) in intracellular signaling and provide the first direct evidence of acute in vivo regulation of CFTR dephosphorylation activity. We show that cytosolic K(+) concentration ([K(+)](c)) declines as a function of increasing cellular NaCl content at the onset of absorptive activity. Declining [K(+)](c) cause parallel deactivation of CFTR by dephosphorylation, thereby limiting apical influx of Cl(-) (and its co-ion Na(+)) until [K(+)](c) is stabilized. We surmise that [K(+)](c) stabilizes when Na(+) influx decreases to a level equal to its efflux through the basolateral Na(+)-K(+) pump thereby preventing disruptive changes in cell volume.
Reddy
M M
MM
Department of Pediatrics, 0831 University of California, San Diego School of Medicine, 9500 Gilman Dr., La Jolla, 92093-0831, USA. mmr@ucsd.edu
Quinton
P M
PM
D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D008297:Male; D019319:Okadaic Acid / Q000737:chemistry / Q000378:metabolism; D011188:Potassium / Q000378:metabolism / Q000502:physiology*; D015221:Potassium Channels / Q000378:metabolism; D013545:Sweat Glands / Q000378:metabolism*
C505032:CFTR protein, human; D015221:Potassium Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D019319:Okadaic Acid; D000242:Cyclic AMP; D011188:Potassium