Na(+) sensitivity of ROMK1 K(+) channel: role of the Na(+)/H(+) antiporter

J Membr Biol. 1999 Nov 1;172(1):67-76. doi: 10.1007/s002329900584.


To examine the extracellular Na(+) sensitivity of a renal inwardly rectifying K(+) channel, we performed electrophysiological experiments on Xenopus oocytes or a human kidney cell line, HEK293, in which we had expressed the cloned renal K(+) channel, ROMK1 (Kir1. 1). When extracellular Na(+) was removed, the whole-cell ROMK1 currents were markedly suppressed in both the oocytes and HEK293 cells. Single-channel ROMK1 activities recorded in the cell-attached patch on the oocyte were not affected by removal of Na(+) from the pipette solution. However, macro-patch ROMK1 currents recorded on the oocyte were significantly suppressed by Na(+) removal from the bath solution. A blocker of Na(+)/H(+) antiporters, amiloride, largely inhibited the Na(+) removal-induced suppression of whole-cell ROMK1 currents in the oocytes. The pH-insensitive K80M mutant of ROMK1 was much less sensitive to Na(+) removal. Na(+) removal was found to induce a significant decrease in intracellular pH in the oocytes using H(+)-selective microelectrodes. Coexpression of ROMK1 with NHE3, which is a Na(+)/H(+) antiporter isoform of the kidney apical membrane, conferred increased sensitivity of ROMK1 channels to extracellular Na(+) in both the oocytes and HEK293 cells. Thus, it is concluded that the ROMK1 channel is regulated indirectly by extracellular Na(+), and that the interaction between NHE transporter and ROMK1 channel appears to be involved in the mechanism of Na(+) sensitivity of ROMK1 channel via regulating intracellular pH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Female
  • Humans
  • In Vitro Techniques
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Patch-Clamp Techniques
  • Potassium Channels / drug effects
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Potassium Channels, Inwardly Rectifying*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sodium / metabolism*
  • Sodium / pharmacology
  • Sodium-Hydrogen Exchangers / metabolism*
  • Xenopus


  • KCNJ1 protein, human
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Recombinant Proteins
  • Sodium-Hydrogen Exchangers
  • Sodium