BKIP-1, an auxiliary subunit critical to SLO-1 function, inhibits SLO-2 potassium channel in vivo

Sci Rep. 2017 Dec 19;7(1):17843. doi: 10.1038/s41598-017-18052-z.

Abstract

Auxiliary subunits are often needed to tailor K+ channel functional properties and expression levels. Many auxiliary subunits have been identified for mammalian Slo1, a high-conductance K+ channel gated by voltage and Ca2+. Experiments with heterologous expression systems show that some of the identified Slo1 auxiliary subunits can also regulate other Slo K+ channels. However, it is unclear whether a single auxiliary subunit may regulate more than one Slo channel in native tissues. BKIP-1, an auxiliary subunit of C. elegans SLO-1, facilitates SLO-1 membrane trafficking and regulates SLO-1 function in neurons and muscle cells. Here we show that BKIP-1 also serves as an auxiliary subunit of C. elegans SLO-2, a high-conductance K+ channel gated by membrane voltage and cytosolic Cl- and Ca2+. Comparisons of whole-cell and single-channel SLO-2 currents in native neurons and muscle cells between worm strains with and without BKIP-1 suggest that BKIP-1 reduces chloride sensitivity, activation rate, and single-channel open probability of SLO-2. Bimolecular fluorescence complementation assays indicate that BKIP-1 interacts with SLO-2 carboxyl terminal. Thus, BKIP-1 may serve as an auxiliary subunit of SLO-2. BKIP-1 appears to be the first example that a single auxiliary subunit exerts opposite effects on evolutionarily related channels in the same cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / metabolism*
  • Calcium / metabolism
  • Cell Membrane / metabolism
  • Cytosol / metabolism
  • Large-Conductance Calcium-Activated Potassium Channels / metabolism*
  • Membrane Transport Proteins / metabolism*
  • Neurons / metabolism
  • Potassium Channels / metabolism
  • Protein Subunits / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Large-Conductance Calcium-Activated Potassium Channels
  • Membrane Transport Proteins
  • Potassium Channels
  • Protein Subunits
  • SLO-2 protein, C elegans
  • slo-1 protein, C elegans
  • Calcium