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Glutamate-activated BK channel complexes formed with NMDA receptors.

Proceedings of the National Academy of Sciences of the United States of America (2018-09-06)
Jiyuan Zhang, Xin Guan, Qin Li, Andrea L Meredith, Hui-Lin Pan, Jiusheng Yan
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 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Glutamate Receptor NMDAR1 (NR1) antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-NMDAR1 Antibody, clone 1.17.2.6, rabbit monoclonal, clone 1.17.2.6, from rabbit, unconjugated
Sigma-Aldrich
Anti-GRIN2B antibody produced in rabbit, affinity isolated antibody
Millipore
ANTI-FLAG® antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-NMDAR2A Antibody, serum, Chemicon®