Pre-synaptic HCN1 channels regulate excitatory neurotransmission at select cortical synapses by altering CaV3.2 Ca2+ channel activity.

Zhuo Huang (1) , Rafael Lujan (1) , Ivan Kadurin (1) , Victor N Uebele (1) , John J Renger (1) , Annette C. Dolphin (1) , Mala Shah (1)

1 Department of Pharmacology

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 play an important role in regulating synaptic potential integration and plasticity. Here, we demonstrate that HCN1 subunits are also localized to the active zone of mature asymmetric synaptic terminals targeting mouse entorhinal cortical layer III pyramidal neurons. We found that HCN channels inhibit glutamate synaptic release by suppressing the activity of low threshold voltage-gated T- (CaV3.2) type Ca2+ channels. In agreement, electron microscopy showed the co-localisation of pre-synaptic HCN1 and CaV3.2 subunit. This represents a novel mechanism by which HCN channels regulate synaptic strength and thereby neural information processing and network excitability.

Mots clés: Channels; Synaptic Transmission; Neurophysiology

Zhuo Huang, Rafael Lujan, Ivan Kadurin, Victor N Uebele, John J Renger, et al.. Pre-synaptic HCN1 channels regulate excitatory neurotransmission at select cortical synapses by altering CaV3.2 Ca2+ channel activity.. Nature Neuroscience, 2011, ⟨10.1038/nn.2757⟩. ⟨hal-00617339⟩