Modulation of sensory neuron potassium conductances by anandamide indicates roles for metabolites

R M Evans, K N Wease, C J MacDonald, H A Khairy, R A Ross, R H Scott

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background and purpose: The endogenous cannabinoid anandamide (AEA) acts at cannabinoid (CB1) and vanilloid (TRPV1) receptors. AEA also shows antinociceptive properties; although the underlying mechanism for this is not fully understood, both CB1 and TRPV1 may be involved. Voltage-activated Ca2+ channels in rat-cultured dorsal root ganglion (DRG) neurons are modulated by AEA. However, AEA in different populations of neurons enhanced or attenuated KCl-evoked Ca2+ influx; these effects were linked with soma size. The aim of this study was to determine how AEA or its metabolites might produce these variable responses.

Experimental approach: The whole cell patch-clamp technique and fura-2 Ca2+ imaging were used to characterize the actions of AEA on action potential firing and voltage-activated K+ currents and to determine whether AEA metabolism plays any role in its effects on cultured DRG neurons.

Key results: AEA attenuated multiple action potential firing evoked by 300 ms depolarizing current commands in a subpopulation of DRG neurons. Application of 1 mu M AEA attenuated voltage-activated K+ currents and the recovery of KCl-evoked Ca2+ transients. The insensitivity of these responses to the CB1 receptor antagonist rimonabant (100 nM) and preincubation of DRG neurons with pertussis toxin suggested that these actions are not CB1 receptor-mediated. Preincubating DRG neurons with the fatty acid amide hydrolase (FAAH) inhibitor phenylmethylsulphonyl fluoride (PMSF) attenuated the inhibitory actions of AEA on K+ currents and Ca2+ influx.

Conclusion and implications: These data suggest that the products of AEA metabolism by FAAH contribute to the attenuation of K+ conductances and altered excitability of cultured sensory neurons.

Original languageEnglish
Pages (from-to)480-492
Number of pages13
JournalBritish Journal of Pharmacology
Volume154
Issue number2
Early online date31 Mar 2008
DOIs
Publication statusPublished - May 2008

Keywords

  • cannabinoids
  • sensory neurons
  • potassium channels
  • anandamide
  • fatty acid amide hydrolase
  • phenylmethylsulphonylfluoride
  • arachidonic acid
  • pain
  • calcium-channel currents
  • in-situ hybridization
  • nerve growth-factor
  • cannabinoid receptor
  • hippocampal-neurons
  • DRG neurons
  • cells
  • K+
  • inhibition

Cite this

Evans, R. M., Wease, K. N., MacDonald, C. J., Khairy, H. A., Ross, R. A., & Scott, R. H. (2008). Modulation of sensory neuron potassium conductances by anandamide indicates roles for metabolites. British Journal of Pharmacology, 154(2), 480-492. https://doi.org/10.1038/bjp.2008.93

Modulation of sensory neuron potassium conductances by anandamide indicates roles for metabolites. / Evans, R M; Wease, K N; MacDonald, C J; Khairy, H A; Ross, R A; Scott, R H.

In: British Journal of Pharmacology, Vol. 154, No. 2, 05.2008, p. 480-492.

Research output: Contribution to journalArticle

Evans, RM, Wease, KN, MacDonald, CJ, Khairy, HA, Ross, RA & Scott, RH 2008, 'Modulation of sensory neuron potassium conductances by anandamide indicates roles for metabolites', British Journal of Pharmacology, vol. 154, no. 2, pp. 480-492. https://doi.org/10.1038/bjp.2008.93
Evans, R M ; Wease, K N ; MacDonald, C J ; Khairy, H A ; Ross, R A ; Scott, R H. / Modulation of sensory neuron potassium conductances by anandamide indicates roles for metabolites. In: British Journal of Pharmacology. 2008 ; Vol. 154, No. 2. pp. 480-492.
@article{297bc8f4fb9a49d99ac7212d9fcafb29,
title = "Modulation of sensory neuron potassium conductances by anandamide indicates roles for metabolites",
abstract = "Background and purpose: The endogenous cannabinoid anandamide (AEA) acts at cannabinoid (CB1) and vanilloid (TRPV1) receptors. AEA also shows antinociceptive properties; although the underlying mechanism for this is not fully understood, both CB1 and TRPV1 may be involved. Voltage-activated Ca2+ channels in rat-cultured dorsal root ganglion (DRG) neurons are modulated by AEA. However, AEA in different populations of neurons enhanced or attenuated KCl-evoked Ca2+ influx; these effects were linked with soma size. The aim of this study was to determine how AEA or its metabolites might produce these variable responses.Experimental approach: The whole cell patch-clamp technique and fura-2 Ca2+ imaging were used to characterize the actions of AEA on action potential firing and voltage-activated K+ currents and to determine whether AEA metabolism plays any role in its effects on cultured DRG neurons.Key results: AEA attenuated multiple action potential firing evoked by 300 ms depolarizing current commands in a subpopulation of DRG neurons. Application of 1 mu M AEA attenuated voltage-activated K+ currents and the recovery of KCl-evoked Ca2+ transients. The insensitivity of these responses to the CB1 receptor antagonist rimonabant (100 nM) and preincubation of DRG neurons with pertussis toxin suggested that these actions are not CB1 receptor-mediated. Preincubating DRG neurons with the fatty acid amide hydrolase (FAAH) inhibitor phenylmethylsulphonyl fluoride (PMSF) attenuated the inhibitory actions of AEA on K+ currents and Ca2+ influx.Conclusion and implications: These data suggest that the products of AEA metabolism by FAAH contribute to the attenuation of K+ conductances and altered excitability of cultured sensory neurons.",
keywords = "cannabinoids, sensory neurons, potassium channels, anandamide, fatty acid amide hydrolase, phenylmethylsulphonylfluoride, arachidonic acid, pain, calcium-channel currents, in-situ hybridization, nerve growth-factor, cannabinoid receptor, hippocampal-neurons, DRG neurons, cells, K+, inhibition",
author = "Evans, {R M} and Wease, {K N} and MacDonald, {C J} and Khairy, {H A} and Ross, {R A} and Scott, {R H}",
year = "2008",
month = "5",
doi = "10.1038/bjp.2008.93",
language = "English",
volume = "154",
pages = "480--492",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Modulation of sensory neuron potassium conductances by anandamide indicates roles for metabolites

AU - Evans, R M

AU - Wease, K N

AU - MacDonald, C J

AU - Khairy, H A

AU - Ross, R A

AU - Scott, R H

PY - 2008/5

Y1 - 2008/5

N2 - Background and purpose: The endogenous cannabinoid anandamide (AEA) acts at cannabinoid (CB1) and vanilloid (TRPV1) receptors. AEA also shows antinociceptive properties; although the underlying mechanism for this is not fully understood, both CB1 and TRPV1 may be involved. Voltage-activated Ca2+ channels in rat-cultured dorsal root ganglion (DRG) neurons are modulated by AEA. However, AEA in different populations of neurons enhanced or attenuated KCl-evoked Ca2+ influx; these effects were linked with soma size. The aim of this study was to determine how AEA or its metabolites might produce these variable responses.Experimental approach: The whole cell patch-clamp technique and fura-2 Ca2+ imaging were used to characterize the actions of AEA on action potential firing and voltage-activated K+ currents and to determine whether AEA metabolism plays any role in its effects on cultured DRG neurons.Key results: AEA attenuated multiple action potential firing evoked by 300 ms depolarizing current commands in a subpopulation of DRG neurons. Application of 1 mu M AEA attenuated voltage-activated K+ currents and the recovery of KCl-evoked Ca2+ transients. The insensitivity of these responses to the CB1 receptor antagonist rimonabant (100 nM) and preincubation of DRG neurons with pertussis toxin suggested that these actions are not CB1 receptor-mediated. Preincubating DRG neurons with the fatty acid amide hydrolase (FAAH) inhibitor phenylmethylsulphonyl fluoride (PMSF) attenuated the inhibitory actions of AEA on K+ currents and Ca2+ influx.Conclusion and implications: These data suggest that the products of AEA metabolism by FAAH contribute to the attenuation of K+ conductances and altered excitability of cultured sensory neurons.

AB - Background and purpose: The endogenous cannabinoid anandamide (AEA) acts at cannabinoid (CB1) and vanilloid (TRPV1) receptors. AEA also shows antinociceptive properties; although the underlying mechanism for this is not fully understood, both CB1 and TRPV1 may be involved. Voltage-activated Ca2+ channels in rat-cultured dorsal root ganglion (DRG) neurons are modulated by AEA. However, AEA in different populations of neurons enhanced or attenuated KCl-evoked Ca2+ influx; these effects were linked with soma size. The aim of this study was to determine how AEA or its metabolites might produce these variable responses.Experimental approach: The whole cell patch-clamp technique and fura-2 Ca2+ imaging were used to characterize the actions of AEA on action potential firing and voltage-activated K+ currents and to determine whether AEA metabolism plays any role in its effects on cultured DRG neurons.Key results: AEA attenuated multiple action potential firing evoked by 300 ms depolarizing current commands in a subpopulation of DRG neurons. Application of 1 mu M AEA attenuated voltage-activated K+ currents and the recovery of KCl-evoked Ca2+ transients. The insensitivity of these responses to the CB1 receptor antagonist rimonabant (100 nM) and preincubation of DRG neurons with pertussis toxin suggested that these actions are not CB1 receptor-mediated. Preincubating DRG neurons with the fatty acid amide hydrolase (FAAH) inhibitor phenylmethylsulphonyl fluoride (PMSF) attenuated the inhibitory actions of AEA on K+ currents and Ca2+ influx.Conclusion and implications: These data suggest that the products of AEA metabolism by FAAH contribute to the attenuation of K+ conductances and altered excitability of cultured sensory neurons.

KW - cannabinoids

KW - sensory neurons

KW - potassium channels

KW - anandamide

KW - fatty acid amide hydrolase

KW - phenylmethylsulphonylfluoride

KW - arachidonic acid

KW - pain

KW - calcium-channel currents

KW - in-situ hybridization

KW - nerve growth-factor

KW - cannabinoid receptor

KW - hippocampal-neurons

KW - DRG neurons

KW - cells

KW - K+

KW - inhibition

U2 - 10.1038/bjp.2008.93

DO - 10.1038/bjp.2008.93

M3 - Article

VL - 154

SP - 480

EP - 492

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 2

ER -