Cytosolic Na+ controls and epithelial Na+ channel via the Go guanine nucleotide-binding regulatory protein.
In tight Na+-absorbing epithelial cells, the fate of Na+ entry through amiloride-sensitive apical membrane Na+ channels is matched to basolateral Na+ extrusion so that cell Na+ concentration and volume remain steady. Control of this process by regulation of apical Na+ channels has been attributed to changes in cytosolic Ca2+ concentration or pH, secondary to changes in cytosolic Na+ concentration, although cytosolic Cl- seems also to be involved. Using mouse mandibular gland duct cells, we now demonstrate that increasing cytosolic Na+ concentration inhibits apical Na+ channels independent of changes in cytosolic Ca2+, pH, or Cl-, and the effect is blocked by GDP-beta-S, pertussis toxin, and antibodies against the alpha-subunits of guanine nucleotide-binding regulatory proteins (Go). In contrast, the inhibitory effect of cytosolic anions is blocked by antibodies to inhibitory guanine nucleotide-binding regulatory proteins (Gi1/Gi2. It thus appears that apical Na+ channels are regulated by Go and Gi proteins, the activities of which are controlled, respectively, by cytosolic Na+ and Cl-.
Komwatana
P
P
Department of Physiology, University of Sydney, New South Wales 2006, Australia.
Dinudom
A
A
Young
J A
JA
Cook
D I
DI
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002463:Cell Membrane Permeability; D003600:Cytosol / Q000378:metabolism; D004553:Electric Conductivity; D004848:Epithelium / Q000502:physiology; D019204:GTP-Binding Proteins / Q000276:immunology / Q000502:physiology*; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008954:Models, Biological; D018408:Patch-Clamp Techniques; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013363:Submandibular Gland / Q000166:cytology / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology
D000906:Antibodies; D015222:Sodium Channels; D013873:Thionucleotides; D006153:Guanosine Diphosphate; C023427:guanosine 5'-O-(2-thiodiphosphate); D000584:Amiloride; D012964:Sodium; D019204:GTP-Binding Proteins