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

Huang Z, Lujan R, Martinez-Hernandez J, Lewis AS, Chetkovich DM, Shah MM
J Neurosci. 2012 32 (42): 14835-48

PMID: 23077068 · PMCID: PMC4104472 · DOI:10.1523/JNEUROSCI.1544-12.2012

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. HCN channel trafficking to dendrites is regulated by the protein, TRIP8b. Additionally, altered TRIP8b expression may be one mechanism underlying seizure-induced dendritic HCN channel plasticity. HCN channels, 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, cortical HCN channel 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. We found 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 cortical HCN channels 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.

MeSH Terms (17)

Animals Cerebral Cortex Cyclic Nucleotide-Gated Cation Channels Excitatory Postsynaptic Potentials Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Membrane Proteins Mice Mice, 129 Strain Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Neuronal Plasticity Peroxins Potassium Channels Presynaptic Terminals Protein Transport Random Allocation

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