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Nat Neurosci. 2011 Apr;14(4):478-86. doi: 10.1038/nn.2757. Epub 2011 Feb 27.

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

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1
Department of Pharmacology, The School of Pharmacy, University of London, London, UK.

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.

PMID:
21358644
PMCID:
PMC3068302
DOI:
10.1038/nn.2757
[Indexed for MEDLINE]
Free PMC Article

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