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AMPA Induces NO-Dependent cGMP Signals in Hippocampal and Cortical Neurons via L-Type Voltage-Gated Calcium Channels

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AMPA Induces NO-Dependent cGMP Signals in Hippocampal and Cortical Neurons via L-Type Voltage-Gated Calcium Channels. / Giesen, Jan; Füchtbauer, Ernst Martin; Füchtbauer, Annette; Funke, Klaus; Koesling, Doris; Russwurm, Michael.

In: Cerebral Cortex, Vol. 30, No. 4, 04.2020, p. 2128-2143.

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Giesen, Jan ; Füchtbauer, Ernst Martin ; Füchtbauer, Annette ; Funke, Klaus ; Koesling, Doris ; Russwurm, Michael. / AMPA Induces NO-Dependent cGMP Signals in Hippocampal and Cortical Neurons via L-Type Voltage-Gated Calcium Channels. In: Cerebral Cortex. 2020 ; Vol. 30, No. 4. pp. 2128-2143.

Bibtex

@article{8942af9719914365ae068b27b873c69a,
title = "AMPA Induces NO-Dependent cGMP Signals in Hippocampal and Cortical Neurons via L-Type Voltage-Gated Calcium Channels",
abstract = "The nitric oxide (NO)/cGMP signaling cascade has an established role in synaptic plasticity. However, with conventional methods, the underlying cGMP signals were barely detectable. Here, we set out to confirm the well-known NMDA-induced cGMP increases, to test the impact of AMPA on those signals, and to identify the relevant phosphodiesterases (PDEs) using a more sensitive fluorescence resonance energy transfer (FRET)-based method. Therefore, a {"}knock-in{"} mouse was generated that expresses a FRET-based cGMP indicator (cGi-500) allowing detection of cGMP concentrations between 100 nM and 3 μM. Measurements were performed in cultured hippocampal and cortical neurons as well as acute hippocampal slices. In hippocampal and cortical neurons, NMDA elicited cGMP signals half as high as the ones elicited by exogenous NO. Interestingly, AMPA increased cGMP independently of NMDA receptors and dependent on NO synthase (NOS) activation. NMDA-and AMPA-induced cGMP signals were not additive indicating that both pathways converge on the level of NOS. Accordingly, the same PDEs, PDE1 and PDE2, were responsible for degradation of NMDA-as well as AMPA-induced cGMP signals. Mechanistically, AMPAR induced calcium influx through L-Type voltage-gated calcium channels leading to NOS and finally NO-sensitive guanylyl cyclase activation. Our results demonstrate that in addition to NMDA also AMPA triggers endogenous NO formation and hence cGMP production.",
keywords = "AMPA, cGMP, L-Type calcium channels, nitric oxide, NMDA",
author = "Jan Giesen and F{\"u}chtbauer, {Ernst Martin} and Annette F{\"u}chtbauer and Klaus Funke and Doris Koesling and Michael Russwurm",
year = "2020",
month = apr,
doi = "10.1093/cercor/bhz227",
language = "English",
volume = "30",
pages = "2128--2143",
journal = "Cerebral Cortex",
issn = "1047-3211",
publisher = "Oxford University Press",
number = "4",

}

RIS

TY - JOUR

T1 - AMPA Induces NO-Dependent cGMP Signals in Hippocampal and Cortical Neurons via L-Type Voltage-Gated Calcium Channels

AU - Giesen, Jan

AU - Füchtbauer, Ernst Martin

AU - Füchtbauer, Annette

AU - Funke, Klaus

AU - Koesling, Doris

AU - Russwurm, Michael

PY - 2020/4

Y1 - 2020/4

N2 - The nitric oxide (NO)/cGMP signaling cascade has an established role in synaptic plasticity. However, with conventional methods, the underlying cGMP signals were barely detectable. Here, we set out to confirm the well-known NMDA-induced cGMP increases, to test the impact of AMPA on those signals, and to identify the relevant phosphodiesterases (PDEs) using a more sensitive fluorescence resonance energy transfer (FRET)-based method. Therefore, a "knock-in" mouse was generated that expresses a FRET-based cGMP indicator (cGi-500) allowing detection of cGMP concentrations between 100 nM and 3 μM. Measurements were performed in cultured hippocampal and cortical neurons as well as acute hippocampal slices. In hippocampal and cortical neurons, NMDA elicited cGMP signals half as high as the ones elicited by exogenous NO. Interestingly, AMPA increased cGMP independently of NMDA receptors and dependent on NO synthase (NOS) activation. NMDA-and AMPA-induced cGMP signals were not additive indicating that both pathways converge on the level of NOS. Accordingly, the same PDEs, PDE1 and PDE2, were responsible for degradation of NMDA-as well as AMPA-induced cGMP signals. Mechanistically, AMPAR induced calcium influx through L-Type voltage-gated calcium channels leading to NOS and finally NO-sensitive guanylyl cyclase activation. Our results demonstrate that in addition to NMDA also AMPA triggers endogenous NO formation and hence cGMP production.

AB - The nitric oxide (NO)/cGMP signaling cascade has an established role in synaptic plasticity. However, with conventional methods, the underlying cGMP signals were barely detectable. Here, we set out to confirm the well-known NMDA-induced cGMP increases, to test the impact of AMPA on those signals, and to identify the relevant phosphodiesterases (PDEs) using a more sensitive fluorescence resonance energy transfer (FRET)-based method. Therefore, a "knock-in" mouse was generated that expresses a FRET-based cGMP indicator (cGi-500) allowing detection of cGMP concentrations between 100 nM and 3 μM. Measurements were performed in cultured hippocampal and cortical neurons as well as acute hippocampal slices. In hippocampal and cortical neurons, NMDA elicited cGMP signals half as high as the ones elicited by exogenous NO. Interestingly, AMPA increased cGMP independently of NMDA receptors and dependent on NO synthase (NOS) activation. NMDA-and AMPA-induced cGMP signals were not additive indicating that both pathways converge on the level of NOS. Accordingly, the same PDEs, PDE1 and PDE2, were responsible for degradation of NMDA-as well as AMPA-induced cGMP signals. Mechanistically, AMPAR induced calcium influx through L-Type voltage-gated calcium channels leading to NOS and finally NO-sensitive guanylyl cyclase activation. Our results demonstrate that in addition to NMDA also AMPA triggers endogenous NO formation and hence cGMP production.

KW - AMPA

KW - cGMP

KW - L-Type calcium channels

KW - nitric oxide

KW - NMDA

UR - http://www.scopus.com/inward/record.url?scp=85079491823&partnerID=8YFLogxK

U2 - 10.1093/cercor/bhz227

DO - 10.1093/cercor/bhz227

M3 - Journal article

C2 - 31711126

AN - SCOPUS:85079491823

VL - 30

SP - 2128

EP - 2143

JO - Cerebral Cortex

JF - Cerebral Cortex

SN - 1047-3211

IS - 4

ER -