TRIP8b-independent trafficking and plasticity of adult cortical presynaptic HCN1 channels

Zhuo Huang, Rafael Lujan, Jose Martinez-Hernandez, Alan S. Lewis, Dane M. Chetkovich, Mala M. Shah

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are subthreshold activated voltage-gated ion channels. In the cortex, these channels are predominantly expressed in dendrites where they significantly modify dendritic intrinsic excitability as well synaptic potential shapes and integration.HCNchannel trafficking to dendrites is regulated by the protein, TRIP8b. Additionally, altered TRIP8b expression may be one mechanism underlying seizure-induced dendriticHCNchannel plasticity. HCNchannels, though, are also located in certain mature cortical synaptic terminals, where they play a vital role in modulating synaptic transmission. In this study, using electrophysiological recordings as well as electron microscopy we show that presynaptic, but not dendritic, corticalHCNchannel expression and function is comparable in adult TRIP8b-null mice and wild-type littermates. We further investigated whether presynaptic HCN channels undergo seizure-dependent plasticity.Wefound that, like dendritic channels, wild-type presynaptic HCN channel function was persistently decreased following induction of kainic acid-induced seizures. Since TRIP8b does not affect presynaptic HCN subunit trafficking, seizure-dependent plasticity of these corticalHCNchannels is not conditional upon TRIP8b. Our results, thus, suggest that the molecular mechanisms underlying HCN subunit targeting, expression and plasticity in adult neurons is compartment selective, providing a means by which pre- and postsynaptic processes that are critically dependent upon HCN channel function may be distinctly influenced.

Original languageEnglish (US)
Pages (from-to)14835-14848
Number of pages14
JournalJournal of Neuroscience
Issue number42
StatePublished - Oct 17 2012

ASJC Scopus subject areas

  • Neuroscience(all)


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