Block of Kcnk3 by protons: Evidence that 2-P-domain potassium channel subunits function as homodimers

Coeli M.B. Lopes, Noam Zilberberg, Steve A.N. Goldstein

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

KCNK subunits have two pore-forming P domains and four predicted transmembrane segments. To assess the number of subunits in each pore, we studied external proton block of Kcnk3, a subunit prominent in rodent heart and brain. Consistent with a pore-blocking mechanism, inhibition was dependent on voltage, potassium concentration, and a histidine in the first P domain (P1H). Thus, at pH 6.8 with 20 mM potassium half the current passed by P1H channels was blocked (apparently via two sites ∼10% into the electrical field) whereas channels with an asparagine substitution (P1N) were fully active. Furthermore, pore blockade by barium was sensitive to pH in P1H but not P1N channels. Although linking two Kcnk3 subunits in tandem to produce P1H-P1H and P1N-P1N channels bearing four P domains did not alter these attributes, the mixed tandems P1H-P1N and P1N-P1H were half-blocked at pH ∼6.4, apparently via a single site. This implicates a dimeric structure for Kcnk3 channels with two (and only two) P1 domains in each pore and argues that P2 domains also contribute to pore formation.

Original languageEnglish
Pages (from-to)24449-24452
Number of pages4
JournalJournal of Biological Chemistry
Volume276
Issue number27
DOIs
StatePublished - 6 Jul 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Block of Kcnk3 by protons: Evidence that 2-P-domain potassium channel subunits function as homodimers'. Together they form a unique fingerprint.

Cite this