Glutamate-activated BK channel complexes formed with NMDA receptors

Proc Natl Acad Sci U S A. 2018 Sep 18;115(38):E9006-E9014. doi: 10.1073/pnas.1802567115. Epub 2018 Sep 4.


The large-conductance calcium- and voltage-activated K+ (BK) channel has a requirement of high intracellular free Ca2+ concentrations for its activation in neurons under physiological conditions. The Ca2+ sources for BK channel activation are not well understood. In this study, we showed by coimmunopurification and colocalization analyses that BK channels form complexes with NMDA receptors (NMDARs) in both rodent brains and a heterologous expression system. The BK-NMDAR complexes are broadly present in different brain regions. The complex formation occurs between the obligatory BKα and GluN1 subunits likely via a direct physical interaction of the former's intracellular S0-S1 loop with the latter's cytosolic regions. By patch-clamp recording on mouse brain slices, we observed BK channel activation by NMDAR-mediated Ca2+ influx in dentate gyrus granule cells. BK channels modulate excitatory synaptic transmission via functional coupling with NMDARs at postsynaptic sites of medial perforant path-dentate gyrus granule cell synapses. A synthesized peptide of the BKα S0-S1 loop region, when loaded intracellularly via recording pipette, abolished the NMDAR-mediated BK channel activation and effect on synaptic transmission. These findings reveal the broad expression of the BK-NMDAR complexes in brain, the potential mechanism underlying the complex formation, and the NMDAR-mediated activation and function of postsynaptic BK channels in neurons.

Keywords: BK channel; NMDA receptor; dentate gyrus granule cells; protein interactions; synaptic transmission.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Dentate Gyrus / cytology
  • Dentate Gyrus / physiology
  • Excitatory Postsynaptic Potentials / physiology*
  • Glutamic Acid / metabolism*
  • HEK293 Cells
  • Humans
  • Large-Conductance Calcium-Activated Potassium Channels / genetics
  • Large-Conductance Calcium-Activated Potassium Channels / isolation & purification
  • Large-Conductance Calcium-Activated Potassium Channels / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / metabolism
  • Patch-Clamp Techniques
  • Perforant Pathway / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / isolation & purification
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Synapses / metabolism
  • Synaptic Transmission / physiology


  • Large-Conductance Calcium-Activated Potassium Channels
  • Receptors, N-Methyl-D-Aspartate
  • Recombinant Proteins
  • Glutamic Acid
  • Calcium