Localization of HCN1 channels to presynaptic compartments: novel plasticity that may contribute to hippocampal maturation.
Increasing evidence supports roles for the current mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, I(h), in hippocampal maturation and specifically in the evolving changes of intrinsic properties as well as network responses of hippocampal neurons. Here, we describe a novel developmental plasticity of HCN channel expression in axonal and presynaptic compartments: HCN1 channels were localized to axon terminals of the perforant path (the major hippocampal afferent pathway) of immature rats, where they modulated synaptic efficacy. However, presynaptic expression and functions of the channels disappeared with maturation. This was a result of altered channel transport to the axons, because HCN1 mRNA and protein levels in entorhinal cortex neurons, where the perforant path axons originate, were stable through adulthood. Blocking action potential firing in vitro increased presynaptic expression of HCN1 channels in the perforant path, suggesting that network activity contributed to regulating this expression. These findings support a novel developmentally regulated axonal transport of functional ion channels and suggest a role for HCN1 channel-mediated presynaptic I(h) in hippocampal maturation.
Bender
Roland A
RA
Department of Anatomy, University of California, Irvine, Irvine, California 92697-4475, USA. r.bender@uke.uni-hamburg.de
Kirschstein
Timo
T
Kretz
Oliver
O
Brewster
Amy L
AL
Richichi
Cristina
C
Rüschenschmidt
Christiane
C
Shigemoto
Ryuichi
R
Beck
Heinz
H
Frotscher
Michael
M
Baram
Tallie Z
TZ
D000818:Animals; D001370:Axonal Transport / Q000502:physiology; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D002451:Cell Compartmentation / Q000502:physiology; D054815:Cyclic Nucleotide-Gated Cation Channels; D015536:Down-Regulation / Q000502:physiology; D018728:Entorhinal Cortex / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development* / Q000502:physiology*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D008854:Microscopy, Electron; D009434:Neural Pathways; D009473:Neuronal Plasticity / Q000502:physiology*; D019580:Perforant Pathway / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism*; D011247:Pregnancy; D017729:Presynaptic Terminals / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley
D054815:Cyclic Nucleotide-Gated Cation Channels; C578667:Hcn1 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels