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Presynaptic HCN1 channels regulate Cav3.2 activity and neurotransmission at select cortical synapses.

Nature neuroscience | 2011

The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are subthreshold, voltage-gated ion channels that are highly expressed in hippocampal and cortical pyramidal cell dendrites, where they are important for regulating synaptic potential integration and plasticity. We found that HCN1 subunits are also localized to the active zone of mature asymmetric synaptic terminals targeting mouse entorhinal cortical layer III pyramidal neurons. HCN channels inhibited glutamate synaptic release by suppressing the activity of low-threshold voltage-gated T-type (Ca(V)3.2) Ca²(+) channels. Consistent with this, electron microscopy revealed colocalization of presynaptic HCN1 and Ca(V)3.2 subunit. This represents a previously unknown mechanism by which HCN channels regulate synaptic strength and thereby neural information processing and network excitability.

Pubmed ID: 21358644 RIS Download

Research resources used in this publication

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Associated grants

  • Agency: Wellcome Trust, United Kingdom
    Id: 087363
  • Agency: Wellcome Trust, United Kingdom
    Id: WT087363MA
  • Agency: NCI NIH HHS, United States
    Id: P01 CA095616
  • Agency: Medical Research Council, United Kingdom
    Id: G0700369(81482)
  • Agency: Medical Research Council, United Kingdom
    Id: G0700369
  • Agency: NINDS NIH HHS, United States
    Id: U24NS050606
  • Agency: Medical Research Council, United Kingdom
    Id: G0801756
  • Agency: NINDS NIH HHS, United States
    Id: U24 NS050606
  • Agency: European Research Council, International
    Id: 260725

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pClamp (tool)

RRID:SCR_011323

Software suite for electrophysiology data acquisition and analysis by Molecular Devices. Used for the control and recording of voltage clamp, current clamp, and patch clamp experiments. The software suite consists of Clampex 11 Software for data acquisition, AxoScope 11 Software for background recording, Clampfit 11 Software for data analysis, and optional Clampfit Advanced Analysis Module for sophisticated and streamlined analysis.

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NeuroMab (tool)

RRID:SCR_003086

A national mouse monoclonal antibody generating resource for biochemical and immunohistochemical applications in mammalian brain. NeuroMabs are generated from mice immunized with synthetic and recombinant immunogens corresponding to components of the neuronal proteome as predicted from genomic and other large-scale cloning efforts. Comprehensive biochemical and immunohistochemical analyses of human, primate and non-primate mammalian brain are incorporated into the initial NeuroMab screening procedure. This yields a subset of mouse mAbs that are optimized for use in brain (i.e. NeuroMabs): for immunocytochemical-based imaging studies of protein localization in adult, developing and pathological brain samples, for biochemical analyses of subunit composition and post-translational modifications of native brain proteins, and for proteomic analyses of native brain protein networks. The NeuroMab facility was initially funded with a five-year U24 cooperative grant from NINDS and NIMH. The initial goal of the facility for this funding period is to generate a library of novel NeuroMabs against neuronal proteins, initially focusing on membrane proteins (receptors/channels/transporters), synaptic proteins, other neuronal signaling molecules, and proteins with established links to disease states. The scope of the facility was expanded with supplements from the NIH Blueprint for Neuroscience Research to include neurodevelopmental targets, the NIH Roadmap for Medical Research to include epigenetics targets, and NIH Office of Rare Diseases Research to include rare disease targets. These NeuroMabs will then be produced on a large scale and made available to the neuroscience research community on an inexpensive basis as tissue culture supernatants or purified immunoglobulin by Antibodies Inc. The UC Davis/NIH NeuroMab Facility makes NeuroMabs available directly to end users and is unable to accommodate sales to distributors for third party distribution. Note, NeuroMab antibodies are now offered through antibodiesinc.

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ImageQuant (tool)

RRID:SCR_014246

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HCN1 ion channel (antibody)

RRID:AB_10672848

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Anti-Cav3.2 Ca2+ Channel Antibody (antibody)

RRID:AB_2315827

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