Ca2+ and pH regulation of K+ channels in membrane vesicles of rabbit proximal tubule.
The effect of Ca2+ and pH on the renal epithelial K+ channel was investigated by measuring the Ba2(+)-sensitive 86Rb+ fluxes in membrane vesicles from pars convoluta of rabbit proximal tubule. It was found that the presence of nanomolar concentrations of Ca2+ in the internal compartment (cytoplasmic) of the vesicles ([Ca2+]i) substantially lowered the channel-mediated flux. Ba2(+)-sensitive 86Rb+ uptake was completely blocked by 10 microM [Ca2+]i. This inhibitory effect of Ca2+ was strongly dependent on pH. Thus 0.1 microM [Ca2+]i produced a maximal inhibition of 86Rb+ uptake at pH greater than 7.4 but had no effect at pH less than 7.0. The tracer fluxes measured in the absence of Ca2+ were pH independent over this range. The data are compatible with the model that Ca2+ blocks K+ channels by binding to a site composed of one or several deprotonated groups. The protonation of any one of these groups prevents Ca2+ from binding to this site but does not by itself block transport.
Jacobsen
C
C
Institute of Medical Biochemistry, University of Aarhus, Denmark.
Mollerup
S
S
Sheikh
M I
MI
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D006859:Hydrogen / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000648:ultrastructure; D015636:Magnesium Chloride / Q000494:pharmacology; D008566:Membranes / Q000378:metabolism; D009994:Osmolar Concentration; D015221:Potassium Channels / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D012413:Rubidium / Q000493:pharmacokinetics; D013997:Time Factors
D015221:Potassium Channels; D015636:Magnesium Chloride; D001464:Barium; D011189:Potassium Chloride; D006859:Hydrogen; D012413:Rubidium; D002118:Calcium