Differential Distribution and Function of Hyperpolarization-Activated Channels in Sensory Neurons and Mechanosensitive Fibers

Thanh N. Doan, Kevin Stephans, Angelina N. Ramirez, Patricia A. Glazebrook, Michael Andresen, Diana L. Kunze

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Sensory neurons express hyperpolarization-activated currents (I H) that differ in magnitude and kinetics within the populations. We investigated the structural basis for these differences and explored the functional role of the IH channels in sensory neurons isolated from rat nodose ganglia. Immunohistochemical studies demonstrated a differential distribution of hyperpolarization-activated cyclic nucleotide-gated (HCN) protein (HCN1, HCN2, HCN4) in sensory neurons and peripheral terminals. HCN2 and HCN4 immunoreactivity was present in all nodose neurons. In contrast, only 20% of the total population expressed HCN1 immunoreactivity. HCN1 did not colocalize with IB4 (a marker for C-type neurons), and only 15% of HCN1-positive neurons colocalized with immunoreactivity for the vanilloid receptor VR1, another protein associated primarily with C-type neurons. Therefore, most HCN1-containing neurons were A-type neurons. In further support, HCN1 was present in the mechanosensitive terminals of myelinated but not unmyelinated sensory fibers, whereas HCN2 and HCN4 were present in receptor terminals of both myelinated and unmyelinated fibers. In voltage-clamp studies, cell permeant cAMP analogs shifted the activation curve for IH to depolarized potentials in C-type neurons but not A-type neurons. In current-clamp recording, CsCl, which inhibits only IH in nodose neurons, hyperpolarized the resting membrane potential from -63 ± 1 to -73 ± 2mV and nearly doubled the input resistance from 1.3 to 2.2 GΩ. In addition, action potentials were initiated at lower depolarizing current injections in the presence of CsCl. At the sensory receptor terminal, CsCl decreased the threshold pressure for initiation of mechanoreceptor discharge. Therefore, elimination of the IH increases excitability of both the soma and the peripheral sensory terminals.

Original languageEnglish (US)
Pages (from-to)3335-3343
Number of pages9
JournalJournal of Neuroscience
Volume24
Issue number13
DOIs
StatePublished - Mar 31 2004

Fingerprint

Sensory Receptor Cells
Neurons
Nodose Ganglion
Mechanoreceptors
Cyclic Nucleotides
Carisoprodol
Membrane Potentials
Population
Action Potentials
Proteins
Pressure
Injections

Keywords

  • Baroreceptors
  • HCN1
  • HCN2
  • HCN4
  • I
  • Nodose
  • Sensory

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Differential Distribution and Function of Hyperpolarization-Activated Channels in Sensory Neurons and Mechanosensitive Fibers. / Doan, Thanh N.; Stephans, Kevin; Ramirez, Angelina N.; Glazebrook, Patricia A.; Andresen, Michael; Kunze, Diana L.

In: Journal of Neuroscience, Vol. 24, No. 13, 31.03.2004, p. 3335-3343.

Research output: Contribution to journalArticle

Doan, Thanh N. ; Stephans, Kevin ; Ramirez, Angelina N. ; Glazebrook, Patricia A. ; Andresen, Michael ; Kunze, Diana L. / Differential Distribution and Function of Hyperpolarization-Activated Channels in Sensory Neurons and Mechanosensitive Fibers. In: Journal of Neuroscience. 2004 ; Vol. 24, No. 13. pp. 3335-3343.
@article{07f6694db44d4d0ba0b28917afe98c54,
title = "Differential Distribution and Function of Hyperpolarization-Activated Channels in Sensory Neurons and Mechanosensitive Fibers",
abstract = "Sensory neurons express hyperpolarization-activated currents (I H) that differ in magnitude and kinetics within the populations. We investigated the structural basis for these differences and explored the functional role of the IH channels in sensory neurons isolated from rat nodose ganglia. Immunohistochemical studies demonstrated a differential distribution of hyperpolarization-activated cyclic nucleotide-gated (HCN) protein (HCN1, HCN2, HCN4) in sensory neurons and peripheral terminals. HCN2 and HCN4 immunoreactivity was present in all nodose neurons. In contrast, only 20{\%} of the total population expressed HCN1 immunoreactivity. HCN1 did not colocalize with IB4 (a marker for C-type neurons), and only 15{\%} of HCN1-positive neurons colocalized with immunoreactivity for the vanilloid receptor VR1, another protein associated primarily with C-type neurons. Therefore, most HCN1-containing neurons were A-type neurons. In further support, HCN1 was present in the mechanosensitive terminals of myelinated but not unmyelinated sensory fibers, whereas HCN2 and HCN4 were present in receptor terminals of both myelinated and unmyelinated fibers. In voltage-clamp studies, cell permeant cAMP analogs shifted the activation curve for IH to depolarized potentials in C-type neurons but not A-type neurons. In current-clamp recording, CsCl, which inhibits only IH in nodose neurons, hyperpolarized the resting membrane potential from -63 ± 1 to -73 ± 2mV and nearly doubled the input resistance from 1.3 to 2.2 GΩ. In addition, action potentials were initiated at lower depolarizing current injections in the presence of CsCl. At the sensory receptor terminal, CsCl decreased the threshold pressure for initiation of mechanoreceptor discharge. Therefore, elimination of the IH increases excitability of both the soma and the peripheral sensory terminals.",
keywords = "Baroreceptors, HCN1, HCN2, HCN4, I, Nodose, Sensory",
author = "Doan, {Thanh N.} and Kevin Stephans and Ramirez, {Angelina N.} and Glazebrook, {Patricia A.} and Michael Andresen and Kunze, {Diana L.}",
year = "2004",
month = "3",
day = "31",
doi = "10.1523/JNEUROSCI.5156-03.2004",
language = "English (US)",
volume = "24",
pages = "3335--3343",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "13",

}

TY - JOUR

T1 - Differential Distribution and Function of Hyperpolarization-Activated Channels in Sensory Neurons and Mechanosensitive Fibers

AU - Doan, Thanh N.

AU - Stephans, Kevin

AU - Ramirez, Angelina N.

AU - Glazebrook, Patricia A.

AU - Andresen, Michael

AU - Kunze, Diana L.

PY - 2004/3/31

Y1 - 2004/3/31

N2 - Sensory neurons express hyperpolarization-activated currents (I H) that differ in magnitude and kinetics within the populations. We investigated the structural basis for these differences and explored the functional role of the IH channels in sensory neurons isolated from rat nodose ganglia. Immunohistochemical studies demonstrated a differential distribution of hyperpolarization-activated cyclic nucleotide-gated (HCN) protein (HCN1, HCN2, HCN4) in sensory neurons and peripheral terminals. HCN2 and HCN4 immunoreactivity was present in all nodose neurons. In contrast, only 20% of the total population expressed HCN1 immunoreactivity. HCN1 did not colocalize with IB4 (a marker for C-type neurons), and only 15% of HCN1-positive neurons colocalized with immunoreactivity for the vanilloid receptor VR1, another protein associated primarily with C-type neurons. Therefore, most HCN1-containing neurons were A-type neurons. In further support, HCN1 was present in the mechanosensitive terminals of myelinated but not unmyelinated sensory fibers, whereas HCN2 and HCN4 were present in receptor terminals of both myelinated and unmyelinated fibers. In voltage-clamp studies, cell permeant cAMP analogs shifted the activation curve for IH to depolarized potentials in C-type neurons but not A-type neurons. In current-clamp recording, CsCl, which inhibits only IH in nodose neurons, hyperpolarized the resting membrane potential from -63 ± 1 to -73 ± 2mV and nearly doubled the input resistance from 1.3 to 2.2 GΩ. In addition, action potentials were initiated at lower depolarizing current injections in the presence of CsCl. At the sensory receptor terminal, CsCl decreased the threshold pressure for initiation of mechanoreceptor discharge. Therefore, elimination of the IH increases excitability of both the soma and the peripheral sensory terminals.

AB - Sensory neurons express hyperpolarization-activated currents (I H) that differ in magnitude and kinetics within the populations. We investigated the structural basis for these differences and explored the functional role of the IH channels in sensory neurons isolated from rat nodose ganglia. Immunohistochemical studies demonstrated a differential distribution of hyperpolarization-activated cyclic nucleotide-gated (HCN) protein (HCN1, HCN2, HCN4) in sensory neurons and peripheral terminals. HCN2 and HCN4 immunoreactivity was present in all nodose neurons. In contrast, only 20% of the total population expressed HCN1 immunoreactivity. HCN1 did not colocalize with IB4 (a marker for C-type neurons), and only 15% of HCN1-positive neurons colocalized with immunoreactivity for the vanilloid receptor VR1, another protein associated primarily with C-type neurons. Therefore, most HCN1-containing neurons were A-type neurons. In further support, HCN1 was present in the mechanosensitive terminals of myelinated but not unmyelinated sensory fibers, whereas HCN2 and HCN4 were present in receptor terminals of both myelinated and unmyelinated fibers. In voltage-clamp studies, cell permeant cAMP analogs shifted the activation curve for IH to depolarized potentials in C-type neurons but not A-type neurons. In current-clamp recording, CsCl, which inhibits only IH in nodose neurons, hyperpolarized the resting membrane potential from -63 ± 1 to -73 ± 2mV and nearly doubled the input resistance from 1.3 to 2.2 GΩ. In addition, action potentials were initiated at lower depolarizing current injections in the presence of CsCl. At the sensory receptor terminal, CsCl decreased the threshold pressure for initiation of mechanoreceptor discharge. Therefore, elimination of the IH increases excitability of both the soma and the peripheral sensory terminals.

KW - Baroreceptors

KW - HCN1

KW - HCN2

KW - HCN4

KW - I

KW - Nodose

KW - Sensory

UR - http://www.scopus.com/inward/record.url?scp=1842610918&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1842610918&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.5156-03.2004

DO - 10.1523/JNEUROSCI.5156-03.2004

M3 - Article

C2 - 15056713

AN - SCOPUS:1842610918

VL - 24

SP - 3335

EP - 3343

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 13

ER -