Widespread expression of olfactory cyclic nucleotide-gated channel genes in rat brain: Implications for neuronal signalling

Paul A. Kingston, Frank Zufall, Colin J. Barnstable

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The cyclic nucleotides cAMP and cGMP are important intracellular messengers involved in a wide variety of signal transduction events in the nervous system. It has been proposed that cAMP/cGMP elicit some of their effects through direct gating of a novel class of Ca2+-permeable ion channels that are termed cyclic nucleotide-gated (CNG) channels. Previous studies have identified the expression of a gene encoding one major CNG channel subtype, the olfactory receptor neuron, subunit, in the brain [El- Husseini et al. (1995) NeuroReport 6:1331-1335; Kingston et al. (1996a) Proc. Natl. Acad. Sci. U.S.A. 93:10440-10445; Bradley et al. (1997) J. Neurosci. 17:1993-2085]. We, therefore, proposed that the actions of cAMP/cGMP on neurons in the brain might occur through the activation of these CNG channels. To determine how widespread such a function might be, the regional and cellular distribution of the olfactory CNG channel subunit has been examined in detail. Primers for multiple portions of the olfactory CNG channel were used in polymerase chain reaction (PCR) to amplify cDNA reverse- transcribed from several brain regions. The identities of PCR products were confirmed with Southern blots and by sequencing. In situ hybridization experiments demonstrated localization of CNG channel mRNA in discrete neuronal populations throughout the brain. In agreement with previous work, relatively strong hybridization signals are present in neuronal cell bodies of the cerebellum, olfactory bulb, cerebral cortex, and brainstem. Additionally, somewhat lesser signals are found in thalamus, hypothalamus, midbrain, and spinal cord while no hybridization signal was detectable in the caudate nucleus. This surprisingly wide distribution throughout the rat brain strengthens the hypothesis that CNG channels may influence numerous processes as downstream effectors of cyclic nucleotide cascades. Interestingly, the distribution of CNG channels is very similar to that of the nitric oxide/cGMP system, suggesting that one function of CNG channels in the brain could be to link diffusible messengers to elevated Ca2+ entry into neurons.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalSynapse
Volume32
Issue number1
DOIs
StatePublished - Mar 22 1999

Fingerprint

Cyclic Nucleotide-Gated Cation Channels
Brain
Genes
Cyclic Nucleotides
Olfactory Receptor Neurons
Neurons
Polymerase Chain Reaction
Caudate Nucleus
Olfactory Bulb
Mesencephalon
Southern Blotting
Thalamus
Ion Channels
Cerebral Cortex
Cerebellum
Nervous System
Hypothalamus
Brain Stem
In Situ Hybridization
Signal Transduction

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

@article{eb3d3070c0084a778dad8072862c9fc3,
title = "Widespread expression of olfactory cyclic nucleotide-gated channel genes in rat brain: Implications for neuronal signalling",
abstract = "The cyclic nucleotides cAMP and cGMP are important intracellular messengers involved in a wide variety of signal transduction events in the nervous system. It has been proposed that cAMP/cGMP elicit some of their effects through direct gating of a novel class of Ca2+-permeable ion channels that are termed cyclic nucleotide-gated (CNG) channels. Previous studies have identified the expression of a gene encoding one major CNG channel subtype, the olfactory receptor neuron, subunit, in the brain [El- Husseini et al. (1995) NeuroReport 6:1331-1335; Kingston et al. (1996a) Proc. Natl. Acad. Sci. U.S.A. 93:10440-10445; Bradley et al. (1997) J. Neurosci. 17:1993-2085]. We, therefore, proposed that the actions of cAMP/cGMP on neurons in the brain might occur through the activation of these CNG channels. To determine how widespread such a function might be, the regional and cellular distribution of the olfactory CNG channel subunit has been examined in detail. Primers for multiple portions of the olfactory CNG channel were used in polymerase chain reaction (PCR) to amplify cDNA reverse- transcribed from several brain regions. The identities of PCR products were confirmed with Southern blots and by sequencing. In situ hybridization experiments demonstrated localization of CNG channel mRNA in discrete neuronal populations throughout the brain. In agreement with previous work, relatively strong hybridization signals are present in neuronal cell bodies of the cerebellum, olfactory bulb, cerebral cortex, and brainstem. Additionally, somewhat lesser signals are found in thalamus, hypothalamus, midbrain, and spinal cord while no hybridization signal was detectable in the caudate nucleus. This surprisingly wide distribution throughout the rat brain strengthens the hypothesis that CNG channels may influence numerous processes as downstream effectors of cyclic nucleotide cascades. Interestingly, the distribution of CNG channels is very similar to that of the nitric oxide/cGMP system, suggesting that one function of CNG channels in the brain could be to link diffusible messengers to elevated Ca2+ entry into neurons.",
author = "Kingston, {Paul A.} and Frank Zufall and Barnstable, {Colin J.}",
year = "1999",
month = "3",
day = "22",
doi = "10.1002/(SICI)1098-2396(199904)32:1<1::AID-SYN1>3.0.CO;2-M",
language = "English (US)",
volume = "32",
pages = "1--12",
journal = "Synapse",
issn = "0887-4476",
publisher = "Wiley-Liss Inc.",
number = "1",

}

Widespread expression of olfactory cyclic nucleotide-gated channel genes in rat brain : Implications for neuronal signalling. / Kingston, Paul A.; Zufall, Frank; Barnstable, Colin J.

In: Synapse, Vol. 32, No. 1, 22.03.1999, p. 1-12.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Widespread expression of olfactory cyclic nucleotide-gated channel genes in rat brain

T2 - Implications for neuronal signalling

AU - Kingston, Paul A.

AU - Zufall, Frank

AU - Barnstable, Colin J.

PY - 1999/3/22

Y1 - 1999/3/22

N2 - The cyclic nucleotides cAMP and cGMP are important intracellular messengers involved in a wide variety of signal transduction events in the nervous system. It has been proposed that cAMP/cGMP elicit some of their effects through direct gating of a novel class of Ca2+-permeable ion channels that are termed cyclic nucleotide-gated (CNG) channels. Previous studies have identified the expression of a gene encoding one major CNG channel subtype, the olfactory receptor neuron, subunit, in the brain [El- Husseini et al. (1995) NeuroReport 6:1331-1335; Kingston et al. (1996a) Proc. Natl. Acad. Sci. U.S.A. 93:10440-10445; Bradley et al. (1997) J. Neurosci. 17:1993-2085]. We, therefore, proposed that the actions of cAMP/cGMP on neurons in the brain might occur through the activation of these CNG channels. To determine how widespread such a function might be, the regional and cellular distribution of the olfactory CNG channel subunit has been examined in detail. Primers for multiple portions of the olfactory CNG channel were used in polymerase chain reaction (PCR) to amplify cDNA reverse- transcribed from several brain regions. The identities of PCR products were confirmed with Southern blots and by sequencing. In situ hybridization experiments demonstrated localization of CNG channel mRNA in discrete neuronal populations throughout the brain. In agreement with previous work, relatively strong hybridization signals are present in neuronal cell bodies of the cerebellum, olfactory bulb, cerebral cortex, and brainstem. Additionally, somewhat lesser signals are found in thalamus, hypothalamus, midbrain, and spinal cord while no hybridization signal was detectable in the caudate nucleus. This surprisingly wide distribution throughout the rat brain strengthens the hypothesis that CNG channels may influence numerous processes as downstream effectors of cyclic nucleotide cascades. Interestingly, the distribution of CNG channels is very similar to that of the nitric oxide/cGMP system, suggesting that one function of CNG channels in the brain could be to link diffusible messengers to elevated Ca2+ entry into neurons.

AB - The cyclic nucleotides cAMP and cGMP are important intracellular messengers involved in a wide variety of signal transduction events in the nervous system. It has been proposed that cAMP/cGMP elicit some of their effects through direct gating of a novel class of Ca2+-permeable ion channels that are termed cyclic nucleotide-gated (CNG) channels. Previous studies have identified the expression of a gene encoding one major CNG channel subtype, the olfactory receptor neuron, subunit, in the brain [El- Husseini et al. (1995) NeuroReport 6:1331-1335; Kingston et al. (1996a) Proc. Natl. Acad. Sci. U.S.A. 93:10440-10445; Bradley et al. (1997) J. Neurosci. 17:1993-2085]. We, therefore, proposed that the actions of cAMP/cGMP on neurons in the brain might occur through the activation of these CNG channels. To determine how widespread such a function might be, the regional and cellular distribution of the olfactory CNG channel subunit has been examined in detail. Primers for multiple portions of the olfactory CNG channel were used in polymerase chain reaction (PCR) to amplify cDNA reverse- transcribed from several brain regions. The identities of PCR products were confirmed with Southern blots and by sequencing. In situ hybridization experiments demonstrated localization of CNG channel mRNA in discrete neuronal populations throughout the brain. In agreement with previous work, relatively strong hybridization signals are present in neuronal cell bodies of the cerebellum, olfactory bulb, cerebral cortex, and brainstem. Additionally, somewhat lesser signals are found in thalamus, hypothalamus, midbrain, and spinal cord while no hybridization signal was detectable in the caudate nucleus. This surprisingly wide distribution throughout the rat brain strengthens the hypothesis that CNG channels may influence numerous processes as downstream effectors of cyclic nucleotide cascades. Interestingly, the distribution of CNG channels is very similar to that of the nitric oxide/cGMP system, suggesting that one function of CNG channels in the brain could be to link diffusible messengers to elevated Ca2+ entry into neurons.

UR - http://www.scopus.com/inward/record.url?scp=0032975938&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032975938&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1098-2396(199904)32:1<1::AID-SYN1>3.0.CO;2-M

DO - 10.1002/(SICI)1098-2396(199904)32:1<1::AID-SYN1>3.0.CO;2-M

M3 - Article

C2 - 10188632

AN - SCOPUS:0032975938

VL - 32

SP - 1

EP - 12

JO - Synapse

JF - Synapse

SN - 0887-4476

IS - 1

ER -