NMDA receptor–BK channel coupling regulates synaptic plasticity in the barrel cortex

Gómez, Ricardo; Maglio, Laura E.; Gonzalez-Hernandez, Alberto J.; Rivero-Pérez, Belinda; Bartolomé-Martı́n, David; Giráldez, Teresa

doi:10.1073/pnas.2107026118

Cited by 24 publications

(25 citation statements)

References 76 publications

(136 reference statements)

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“…EGTA-insensitive coupling of BK channels with NMDARs was also recently observed in a subset of barrel cortex layer 5 pyramidal neurons (BC-L5PNs) but when NMDA was applied toward basal dendrites instead of soma (Gomez et al, 2021). In a heterologous expression system of HEK293 cells, similar results of BK-NMDAR (GluN1/GluN2A) functional coupling were revealed by whole cell voltage-clamp recording (Zhang et al, 2018).…”

Section: Bk-nmdar Colocalization and Functional Coupling Within The N...supporting

confidence: 65%

“…Postsynaptic BK-NMDAR coupling was also recently reported to occur in the basal dendrites of approximately 40% of BC-L5PNs (Gomez et al, 2021). The application of NMDA toward basal dendrites led to large NMDAR inward and BK channel outward currents recorded in soma, supporting dendritic locations of BK-NMDAR coupling (Gomez et al, 2021).…”

Section: Localization and Roles Of Bk-nmdar Coupling In The Nervous S...mentioning

confidence: 75%

“…With in situ PLA, BKα and GluN1 were found to be colocalized in both the heterologous expression system and, broadly, in different regions of mouse hippocampus (Zhang et al, 2018). Consistent with the sole requirement of GluN1 for protein complex formation with BK channels (Zhang et al, 2018), PLA with HEK293 cells co-expressing BK channels with GluN1/GluN2A or GluN1/GluN2B showed no preference in BK channels' proximity to these 2 types of NMDARs (Gomez et al, 2021). In the dentate gyrus, PLA signals of the BKα-GluN1 complexes were most abundant in the molecular layer region (Zhang et al, 2018), which is consistent with the predominant dendritic distribution of NMDARs.…”

Section: Bk-nmdar Colocalization and Functional Coupling Within The N...mentioning

confidence: 78%

“…The colocalization of BK and NMDARs was probed with an in situ PLA (Zhang et al, 2018;Gomez et al, 2021). PLA displays point-like staining signals only when the 2 epitopes on the interacting proteins for primary antibodies are in proximity (<40 nm) (Soderberg et al, 2006), making PLA a suitable assay for the detection of protein colocalization within the nanodomain.…”

Section: Bk-nmdar Colocalization and Functional Coupling Within The N...mentioning

confidence: 99%

“…In excised inside-out membrane patches of HEK293 cells, BK channel openings at the single channel level were observed upon NMDAR activation using flash photolysis of caged NMDA (Zhang et al, 2018). In HEK293 cells, activation of NMDARs formed by GluN1/GluN2A or GluN1/GluN2B both resulted in large shifts in the apparent voltage dependence of BK channel activation (Gomez et al, 2021).…”

Section: Bk-nmdar Colocalization and Functional Coupling Within The N...mentioning

confidence: 99%

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Structural and Functional Coupling of Calcium-Activated BK Channels and Calcium-Permeable Channels Within Nanodomain Signaling Complexes

2022

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Biochemical and functional studies of ion channels have shown that many of these integral membrane proteins form macromolecular signaling complexes by physically associating with many other proteins. These macromolecular signaling complexes ensure specificity and proper rates of signal transduction. The large-conductance, Ca2+-activated K+ (BK) channel is dually activated by membrane depolarization and increases in intracellular free Ca2+ ([Ca2+]i). The activation of BK channels results in a large K+ efflux and, consequently, rapid membrane repolarization and closing of the voltage-dependent Ca2+-permeable channels to limit further increases in [Ca2+]i. Therefore, BK channel-mediated K+ signaling is a negative feedback regulator of both membrane potential and [Ca2+]i and plays important roles in many physiological processes and diseases. However, the BK channel formed by the pore-forming and voltage- and Ca2+-sensing α subunit alone requires high [Ca2+]i levels for channel activation under physiological voltage conditions. Thus, most native BK channels are believed to co-localize with Ca2+-permeable channels within nanodomains (a few tens of nanometers in distance) to detect high levels of [Ca2+]i around the open pores of Ca2+-permeable channels. Over the last two decades, advancement in research on the BK channel’s coupling with Ca2+-permeable channels including recent reports involving NMDA receptors demonstrate exemplary models of nanodomain structural and functional coupling among ion channels for efficient signal transduction and negative feedback regulation. We hereby review our current understanding regarding the structural and functional coupling of BK channels with different Ca2+-permeable channels.

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Section: Bk-nmdar Colocalization and Functional Coupling Within The N...supporting

confidence: 65%

Section: Localization and Roles Of Bk-nmdar Coupling In The Nervous S...mentioning

confidence: 75%

Section: Bk-nmdar Colocalization and Functional Coupling Within The N...mentioning

confidence: 78%

Section: Bk-nmdar Colocalization and Functional Coupling Within The N...mentioning

confidence: 99%

Section: Bk-nmdar Colocalization and Functional Coupling Within The N...mentioning

confidence: 99%

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Structural and Functional Coupling of Calcium-Activated BK Channels and Calcium-Permeable Channels Within Nanodomain Signaling Complexes

2022

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BK channels sustain neuronal Ca2+ oscillations to support hippocampal long-term potentiation and memory formation

Pham,

Hussein,

Calis

et al. 2023

Cell. Mol. Life Sci.

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Mutations of large conductance Ca2+- and voltage-activated K+ channels (BK) are associated with cognitive impairment. Here we report that CA1 pyramidal neuron-specific conditional BK knock-out (cKO) mice display normal locomotor and anxiety behavior. They do, however, exhibit impaired memory acquisition and retrieval in the Morris Water Maze (MWM) when compared to littermate controls (CTRL). In line with cognitive impairment in vivo, electrical and chemical long-term potentiation (LTP) in cKO brain slices were impaired in vitro. We further used a genetically encoded fluorescent K+ biosensor and a Ca2+-sensitive probe to observe cultured hippocampal neurons during chemical LTP (cLTP) induction. cLTP massively reduced intracellular K+ concentration ([K+]i) while elevating L-Type Ca2+ channel- and NMDA receptor-dependent Ca2+ oscillation frequencies. Both, [K+]i decrease and Ca2+ oscillation frequency increase were absent after pharmacological BK inhibition or in cells lacking BK. Our data suggest that L-Type- and NMDAR-dependent BK-mediated K+ outflow significantly contributes to hippocampal LTP, as well as learning and memory.

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Endogenous Modulators of NMDA Receptor Control Dendritic Field Expansion of Cortical Neurons

et al. 2022

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Impairments of N-methyl-D-aspartate receptor (NMDAR) activity have been implicated in several neuropsychiatric disorders, with pharmacological inhibition of NMDAR-mediated currents and associated neurobehavioral changes considered as a model of schizophrenia. We analyzed the effects of brief and long-term exposure of rat cortical cultures to the most prevalent endogenous modulators of NMDAR (kynurenic acid, pregnenolone sulfate, spermidine, and zinc) on neuronal viability, stimulation-induced release of glutamate, and dendritic morphology with synaptic density. Both, glutamate release and neuronal viability studies revealed no difference between the test and control groups. No differences were also observed in the number of dendritic branching and length, or density of synaptic connections and neuronal soma size. Comparison of the extent of dendritic projections and branching patterns, however, revealed enhanced distal arborization with the expansion of the dendritic area under prolonged treatment of cultures with physiological concentrations of NMDAR modulators, with differences reaching significance in spermidine and pregnenolone sulfate tests. Measurements of the density of glutamatergic synapses showed consistency across all neuronal groups, except those treated with pregnenolone sulfate, which showed a reduction of PSD-95–positive elements. Overall, our data suggest that constitutive glutamatergic activity mediated by NMDAR controls the dendritic field expansion and can influence the integrative properties of cortical neurons.

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NMDA receptor–BK channel coupling regulates synaptic plasticity in the barrel cortex

Cited by 24 publications

References 76 publications

Structural and Functional Coupling of Calcium-Activated BK Channels and Calcium-Permeable Channels Within Nanodomain Signaling Complexes

Structural and Functional Coupling of Calcium-Activated BK Channels and Calcium-Permeable Channels Within Nanodomain Signaling Complexes

BK channels sustain neuronal Ca2+ oscillations to support hippocampal long-term potentiation and memory formation

Endogenous Modulators of NMDA Receptor Control Dendritic Field Expansion of Cortical Neurons

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