TY  - JOUR
AU  - Mobley, A.S.
AU  - Miller, A.M.
AU  - Araneda, R.C.
AU  - Maurer, L.R.
AU  - Müller, F.
AU  - Greer, C.A.
TI  - Hyperpolarization-activated cyclic nucleotide-gated channels in olfactory sensory neurons regulate axon extension and glomerular formation
JO  - The journal of neuroscience
VL  - 30
SN  - 0270-6474
CY  - Washington, DC
PB  - Soc.
M1  - PreJuSER-14281
SP  - 16498 - 16508
PY  - 2010
N1  - This work was funded by National Institutes of Health (NIH)-National Institute on Deafness and Other Communication Disorders and NIH-National Institute on Aging grants (C.A.G.). A.M.M. was supported by Medical Scientist Training Program Grant GM07205 and NIH Grant F30 DC010324. A.S.M. was supported by Neurobiology Training Grant NS 007224-24 and National Research Service Award F32 DC010098-01A1. We thank Drs. L. Rela and M. B. Richard for developing the whole-mount imaging technique in our lab. HCN antibodies were generously provided by Dr. R. Shigemoto, National Institute for Physiological Sciences, Japan.
AB  - Mechanisms influencing the development of olfactory bulb glomeruli are poorly understood. While odor receptors (ORs) play an important role in olfactory sensory neuron (OSN) axon targeting/coalescence (Mombaerts et al., 1996; Wang et al., 1998; Feinstein and Mombaerts, 2004), recent work showed that G protein activation alone is sufficient to induce OSN axon coalescence (Imai et al., 2006; Chesler et al., 2007), suggesting an activity-dependent mechanism in glomerular development. Consistent with these data, OSN axon projections and convergence are perturbed in mice deficient for adenylyl cyclase III, which is downstream from the OR and catalyzes the conversion of ATP to cAMP. However, in cyclic nucleotide-gated (CNG) channel knock-out mice OSN axons are only transiently perturbed (Lin et al., 2000), suggesting that the CNG channel may not be the sole target of cAMP. This prompted us to investigate an alternative channel, the hyperpolarization-activated, cyclic nucleotide-gated cation channel (HCN), as a potential developmental target of cAMP in OSNs. Here, we demonstrate that HCN channels are developmentally precocious in OSNs and therefore are plausible candidates for affecting OSN axon development. Inhibition of HCN channels in dissociated OSNs significantly reduced neurite outgrowth. Moreover, in HCN1 knock-out mice the formation of glomeruli was delayed in parallel with perturbations of axon organization in the olfactory nerve. These data support the hypothesis that the outgrowth and coalescence of OSN axons is, at least in part, subject to activity-dependent mechanisms mediated via HCN channels.
KW  - Animals
KW  - Animals, Newborn
KW  - Antidiarrheals: pharmacology
KW  - Axons: drug effects
KW  - Axons: physiology
KW  - Biophysics: methods
KW  - Cardiotonic Agents: pharmacology
KW  - Cells, Cultured
KW  - Cyclic Nucleotide-Gated Cation Channels: deficiency
KW  - Cyclic Nucleotide-Gated Cation Channels: physiology
KW  - Electric Stimulation: methods
KW  - Embryo, Mammalian
KW  - GAP-43 Protein: metabolism
KW  - Gene Expression Regulation, Developmental: drug effects
KW  - Gene Expression Regulation, Developmental: physiology
KW  - Green Fluorescent Proteins: genetics
KW  - Ion Channels: genetics
KW  - Ion Channels: metabolism
KW  - Loperamide: pharmacology
KW  - Membrane Potentials: drug effects
KW  - Membrane Potentials: genetics
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Mice, Knockout
KW  - Neural Cell Adhesion Molecules: metabolism
KW  - Neurogenesis: drug effects
KW  - Neurogenesis: physiology
KW  - Olfactory Bulb: cytology
KW  - Olfactory Bulb: embryology
KW  - Olfactory Bulb: growth & development
KW  - Patch-Clamp Techniques: methods
KW  - Potassium Channels: deficiency
KW  - Potassium Channels: genetics
KW  - Potassium Channels: metabolism
KW  - Potassium Channels: physiology
KW  - Pyrimidines: pharmacology
KW  - Receptors, Odorant: genetics
KW  - Receptors, Odorant: metabolism
KW  - Sensory Receptor Cells: cytology
KW  - Sensory Receptor Cells: drug effects
KW  - Antidiarrheals (NLM Chemicals)
KW  - Cardiotonic Agents (NLM Chemicals)
KW  - Cyclic Nucleotide-Gated Cation Channels (NLM Chemicals)
KW  - GAP-43 Protein (NLM Chemicals)
KW  - HCN2 potassium channel (NLM Chemicals)
KW  - HCN4 protein, rat (NLM Chemicals)
KW  - Ion Channels (NLM Chemicals)
KW  - Neural Cell Adhesion Molecules (NLM Chemicals)
KW  - Olfr1507 protein, mouse (NLM Chemicals)
KW  - Potassium Channels (NLM Chemicals)
KW  - Pyrimidines (NLM Chemicals)
KW  - Receptors, Odorant (NLM Chemicals)
KW  - hyperpolarization-activated cation channel (NLM Chemicals)
KW  - ICI D2788 (NLM Chemicals)
KW  - Green Fluorescent Proteins (NLM Chemicals)
KW  - Loperamide (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:21147989
C2  - pmc:PMC3393111
UR  - <Go to ISI:>//WOS:000285089100011
DO  - DOI:10.1523/JNEUROSCI.4225-10.2010
UR  - https://juser.fz-juelich.de/record/14281
ER  -