Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system

Diego Alvarez De La Rosa, Ping Zhang, Deren Shao, Fletcher White, Cecilia M. Canessa

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

Acid-sensitive ion channels (ASIC) are proton-gated ion channels expressed in neurons of the mammalian central and peripheral nervous systems. The functional role of these channels is still uncertain, but they have been proposed to constitute mechano-receptors and/or nociceptors. We have raised specific antibodies for ASIC1, ASIC2, ASIC3, and ASIC4 to examine the distribution of these proteins in neurons from dorsal root ganglia (DRG) and to determine their subcellular localization. Western blot analysis demonstrates that all four ASIC proteins are expressed in DRG and sciatic nerve. Immunohistochemical experiments and functional measurements of unitary currents from the ASICs with the patch-clamp technique indicate that ASIC1 localizes to the plasma membrane of small-, medium-, and large-diameter cells, whereas ASIC2 and ASIC3 are preferentially in medium to large cells. Neurons coexpressing ASIC2 and ASIC3 form predominantly heteromeric ASIC2-3 channels. Two spliced forms, ASIC2a and ASIC2b, colocalize in the same population of DRG neurons. Within cells, the ASICs are present mainly on the plasma membrane of the soma and cellular processes. Functional studies indicate that the pH sensitivity for inactivation of ASIC1 is much higher than the one for activation; hence, increases in proton concentration will inactivate the channel. These functional properties and localization in DRG have profound implications for the putative functional roles of ASICs in the nervous system.

Original languageEnglish (US)
Pages (from-to)2326-2331
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number4
DOIs
StatePublished - Feb 19 2002
Externally publishedYes

Fingerprint

Peripheral Nervous System
Spinal Ganglia
Ion Channels
Neurons
Acids
Protons
Cell Membrane
Nociceptors
Carisoprodol
Patch-Clamp Techniques
Sciatic Nerve
Nervous System
Proteins
Central Nervous System
Western Blotting
Antibodies
Population

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system. / De La Rosa, Diego Alvarez; Zhang, Ping; Shao, Deren; White, Fletcher; Canessa, Cecilia M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 4, 19.02.2002, p. 2326-2331.

Research output: Contribution to journalArticle

@article{2983968bde0f4c638670d5171656c7f2,
title = "Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system",
abstract = "Acid-sensitive ion channels (ASIC) are proton-gated ion channels expressed in neurons of the mammalian central and peripheral nervous systems. The functional role of these channels is still uncertain, but they have been proposed to constitute mechano-receptors and/or nociceptors. We have raised specific antibodies for ASIC1, ASIC2, ASIC3, and ASIC4 to examine the distribution of these proteins in neurons from dorsal root ganglia (DRG) and to determine their subcellular localization. Western blot analysis demonstrates that all four ASIC proteins are expressed in DRG and sciatic nerve. Immunohistochemical experiments and functional measurements of unitary currents from the ASICs with the patch-clamp technique indicate that ASIC1 localizes to the plasma membrane of small-, medium-, and large-diameter cells, whereas ASIC2 and ASIC3 are preferentially in medium to large cells. Neurons coexpressing ASIC2 and ASIC3 form predominantly heteromeric ASIC2-3 channels. Two spliced forms, ASIC2a and ASIC2b, colocalize in the same population of DRG neurons. Within cells, the ASICs are present mainly on the plasma membrane of the soma and cellular processes. Functional studies indicate that the pH sensitivity for inactivation of ASIC1 is much higher than the one for activation; hence, increases in proton concentration will inactivate the channel. These functional properties and localization in DRG have profound implications for the putative functional roles of ASICs in the nervous system.",
author = "{De La Rosa}, {Diego Alvarez} and Ping Zhang and Deren Shao and Fletcher White and Canessa, {Cecilia M.}",
year = "2002",
month = "2",
day = "19",
doi = "10.1073/pnas.042688199",
language = "English (US)",
volume = "99",
pages = "2326--2331",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "4",

}

TY - JOUR

T1 - Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system

AU - De La Rosa, Diego Alvarez

AU - Zhang, Ping

AU - Shao, Deren

AU - White, Fletcher

AU - Canessa, Cecilia M.

PY - 2002/2/19

Y1 - 2002/2/19

N2 - Acid-sensitive ion channels (ASIC) are proton-gated ion channels expressed in neurons of the mammalian central and peripheral nervous systems. The functional role of these channels is still uncertain, but they have been proposed to constitute mechano-receptors and/or nociceptors. We have raised specific antibodies for ASIC1, ASIC2, ASIC3, and ASIC4 to examine the distribution of these proteins in neurons from dorsal root ganglia (DRG) and to determine their subcellular localization. Western blot analysis demonstrates that all four ASIC proteins are expressed in DRG and sciatic nerve. Immunohistochemical experiments and functional measurements of unitary currents from the ASICs with the patch-clamp technique indicate that ASIC1 localizes to the plasma membrane of small-, medium-, and large-diameter cells, whereas ASIC2 and ASIC3 are preferentially in medium to large cells. Neurons coexpressing ASIC2 and ASIC3 form predominantly heteromeric ASIC2-3 channels. Two spliced forms, ASIC2a and ASIC2b, colocalize in the same population of DRG neurons. Within cells, the ASICs are present mainly on the plasma membrane of the soma and cellular processes. Functional studies indicate that the pH sensitivity for inactivation of ASIC1 is much higher than the one for activation; hence, increases in proton concentration will inactivate the channel. These functional properties and localization in DRG have profound implications for the putative functional roles of ASICs in the nervous system.

AB - Acid-sensitive ion channels (ASIC) are proton-gated ion channels expressed in neurons of the mammalian central and peripheral nervous systems. The functional role of these channels is still uncertain, but they have been proposed to constitute mechano-receptors and/or nociceptors. We have raised specific antibodies for ASIC1, ASIC2, ASIC3, and ASIC4 to examine the distribution of these proteins in neurons from dorsal root ganglia (DRG) and to determine their subcellular localization. Western blot analysis demonstrates that all four ASIC proteins are expressed in DRG and sciatic nerve. Immunohistochemical experiments and functional measurements of unitary currents from the ASICs with the patch-clamp technique indicate that ASIC1 localizes to the plasma membrane of small-, medium-, and large-diameter cells, whereas ASIC2 and ASIC3 are preferentially in medium to large cells. Neurons coexpressing ASIC2 and ASIC3 form predominantly heteromeric ASIC2-3 channels. Two spliced forms, ASIC2a and ASIC2b, colocalize in the same population of DRG neurons. Within cells, the ASICs are present mainly on the plasma membrane of the soma and cellular processes. Functional studies indicate that the pH sensitivity for inactivation of ASIC1 is much higher than the one for activation; hence, increases in proton concentration will inactivate the channel. These functional properties and localization in DRG have profound implications for the putative functional roles of ASICs in the nervous system.

UR - http://www.scopus.com/inward/record.url?scp=0037133209&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037133209&partnerID=8YFLogxK

U2 - 10.1073/pnas.042688199

DO - 10.1073/pnas.042688199

M3 - Article

VL - 99

SP - 2326

EP - 2331

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 4

ER -