TRIP8b-independent trafficking and plasticity of adult cortical presynaptic HCN1 channels.
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.
Department of Pharmacology, UCL School of Pharmacy, University College London, London, WC1N 1AX, United Kingdom.
Zhuo
Z
Huang
Rafael
R
Lujan
Jose
J
Martinez-Hernandez
Alan S
AS
Lewis
Dane M
DM
Chetkovich
Mala M
MM
Shah
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000648:ultrastructure; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000172:deficiency / Q000378:metabolism* / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology*; D000074401:Peroxins; D015221:Potassium Channels / Q000172:deficiency / Q000378:metabolism* / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D011897:Random Allocation
D054815:Cyclic Nucleotide-Gated Cation Channels; C578666:Hcn1 protein, mouse; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D008565:Membrane Proteins; D000074401:Peroxins; C501732:Pex5l protein, mouse; D015221:Potassium Channels