title: Presynaptic HCN1 channels regulate Cav3.2 activity and neurotransmission at select cortical synapses.
abstract: 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.
authors.affiliation: Department of Pharmacology, The School of Pharmacy, University of London, London, UK.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Huang
authors.forename: Rafael
authors.initials: R
authors.lastname: Lujan
authors.forename: Ivan
authors.initials: I
authors.lastname: Kadurin
authors.forename: Victor N
authors.initials: VN
authors.lastname: Uebele
authors.forename: John J
authors.initials: JJ
authors.lastname: Renger
authors.forename: Annette C
authors.initials: AC
authors.lastname: Dolphin
authors.forename: Mala M
authors.initials: MM
authors.lastname: Shah
mesh_terms: D000818:Animals; D020747:Calcium Channels, T-Type / Q000502:physiology*; D020013:Calcium Signaling / Q000235:genetics / Q000502:physiology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000502:physiology*; D018728:Entorhinal Cortex / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000378:metabolism; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000502:physiology; D009924:Organ Culture Techniques; D015221:Potassium Channels / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D021122:Protein Subunits / Q000502:physiology; D017966:Pyramidal Cells / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*
chemical_list: C479952:CACNA1H protein, human; D020747:Calcium Channels, T-Type; D054815:Cyclic Nucleotide-Gated Cation Channels; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; C578665:HCN1 protein, human; C578666:Hcn1 protein, mouse; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels; D021122:Protein Subunits