Title: Presynaptic HCN1 channels regulate Ca(V)3.2 activity and neurotransmission at select cortical synapses.

Authors: Zhuo Huang, Rafael Lujan, Ivan Kadurin, Victor N Uebele, John J Renger, Annette C Dolphin, Mala M Shah

Journal, date & volume: , 2011 Feb 27 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21358644

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.