Extracellular K+ and intracellular pH allosterically regulate renal Kir1.1 channels.
The channels that control K+ homeostasis by mediating K+ secretion across the apical membrane of renal tubular cells have recently been cloned and designated ROMK1, -2, and -3. Native apical K+ channels are indirectly regulated by the K+ concentration at the basolateral membrane through a cascade of intracellular second messengers. It is shown here that ROMK1 (Kir1.1) channels are also directly regulated by the extracellular (apical) K+ concentration, and that this K+ regulation is coupled to intracellular pH. The K+ regulation and its coupling to pH were assigned to different structural parts of the channel protein. K+ regulation is determined by the core region, which comprises the two hydrophobic segments M1 and M2 and the P region. Decoupling from pH was achieved by exchanging the N terminus of ROMK1 by that of the pH-insensitive channel IRK1 (Kir2.1). These results suggest an allosteric regulation of ROMK1 channels by extracellular K+ and intracellular pH, which may represent a novel link between K+ homeostasis and pH control.
Doi
T
T
Department of Sensory Biophysics, Ear-Nose-and-Throat Hospital of the University of Tübingen, Germany.
Fakler
B
B
Schultz
J H
JH
Schulte
U
U
Brändle
U
U
Weidemann
S
S
Zenner
H P
HP
Lang
F
F
Ruppersberg
J P
JP
D000494:Allosteric Regulation; D000818:Animals; D004594:Electrophysiology / Q000379:methods; D005260:Female; D006706:Homeostasis; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology; D016133:Polymerase Chain Reaction; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology*; D015221:Potassium Channels / Q000096:biosynthesis / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D018075:RNA, Complementary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014982:Xenopus laevis
D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D018075:RNA, Complementary; D011993:Recombinant Fusion Proteins; D011188:Potassium