Glutamate-activated BK channel complexes formed with NMDA receptors

Abstract

Significance Large-conductance BK channels are dually activated by voltage and Ca 2+ and play a powerful integrative role in regulating cellular excitability and Ca 2+ signaling in neurons. However, BK channels have a requirement of high intracellular free Ca 2+ concentrations for activation under physiological conditions, and the Ca 2+ sources for their activation are not well understood. In this work, we establish that BK channels physically form protein complexes with Ca 2+ -permeable NMDA receptors via their obligatory BKα and GluN1 subunits. The activation mechanism and function of postsynaptic BK channels at synapses remain largely unknown. We found that postsynaptic BK channels in medial perforant path-dentate gyrus granule cell synapses are activated by NMDA receptor-mediated Ca 2+ influx and modulate excitatory synaptic transmission.