Glutamate-activated BK channel complexes formed with NMDA receptors

Jiyuan Zhang, Xin Guan, Qin Li, Andrea L. Meredith, Hui Lin Pan, Jiusheng Yan

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

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 BKa 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 BKa 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.

Original languageEnglish (US)
Pages (from-to)E9006-E9014
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number38
DOIs
StatePublished - Sep 18 2018
Externally publishedYes

Keywords

  • BK channel
  • Dentate gyrus granule cells
  • NMDA receptor
  • Protein interactions
  • Synaptic transmission

ASJC Scopus subject areas

  • General

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