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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.

SUBMITTER: Huang Z

PROVIDER: S-EPMC3068302 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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

Huang Zhuo Z Lujan Rafael R Kadurin Ivan I Uebele Victor N VN Renger John J JJ Dolphin Annette C AC Shah Mala M MM

Nature neuroscience 20110227 4

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 rele ...[more]

PMID: 21358644

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