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Dorsal root ganglion neurons innervating skeletal muscle respond to physiological combinations of protons, ATP, and lactate mediated by ASIC, P2X, and TRPV1.
J Neurophysiol. 2008 Sep; 100(3):1184-201.JN

Abstract

The adequate stimuli and molecular receptors for muscle metaboreceptors and nociceptors are still under investigation. We used calcium imaging of cultured primary sensory dorsal root ganglion (DRG) neurons from C57Bl/6 mice to determine candidates for metabolites that could be the adequate stimuli and receptors that could detect these stimuli. Retrograde DiI labeling determined that some of these neurons innervated skeletal muscle. We found that combinations of protons, ATP, and lactate were much more effective than individually applied compounds for activating rapid calcium increases in muscle-innervating dorsal root ganglion neurons. Antagonists for P2X, ASIC, and TRPV1 receptors suggested that these three receptors act together to detect protons, ATP, and lactate when presented together in physiologically relevant concentrations. Two populations of muscle-innervating DRG neurons were found. One responded to low metabolite levels (likely nonnoxious) and used ASIC3, P2X5, and TRPV1 as molecular receptors to detect these metabolites. The other responded to high levels of metabolites (likely noxious) and used ASIC3, P2X4, and TRPV1 as their molecular receptors. We conclude that a combination of ASIC, P2X5 and/or P2X4, and TRPV1 are the molecular receptors used to detect metabolites by muscle-innervating sensory neurons. We further conclude that the adequate stimuli for muscle metaboreceptors and nociceptors are combinations of protons, ATP, and lactate.

Authors+Show Affiliations

Department of Anethesiology, University of Utah School of Medicine, Salt Lake City, UT 84132-2304, USA. alan.light@hsc.utah.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18509077

Citation

Light, Alan R., et al. "Dorsal Root Ganglion Neurons Innervating Skeletal Muscle Respond to Physiological Combinations of Protons, ATP, and Lactate Mediated By ASIC, P2X, and TRPV1." Journal of Neurophysiology, vol. 100, no. 3, 2008, pp. 1184-201.
Light AR, Hughen RW, Zhang J, et al. Dorsal root ganglion neurons innervating skeletal muscle respond to physiological combinations of protons, ATP, and lactate mediated by ASIC, P2X, and TRPV1. J Neurophysiol. 2008;100(3):1184-201.
Light, A. R., Hughen, R. W., Zhang, J., Rainier, J., Liu, Z., & Lee, J. (2008). Dorsal root ganglion neurons innervating skeletal muscle respond to physiological combinations of protons, ATP, and lactate mediated by ASIC, P2X, and TRPV1. Journal of Neurophysiology, 100(3), 1184-201. https://doi.org/10.1152/jn.01344.2007
Light AR, et al. Dorsal Root Ganglion Neurons Innervating Skeletal Muscle Respond to Physiological Combinations of Protons, ATP, and Lactate Mediated By ASIC, P2X, and TRPV1. J Neurophysiol. 2008;100(3):1184-201. PubMed PMID: 18509077.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dorsal root ganglion neurons innervating skeletal muscle respond to physiological combinations of protons, ATP, and lactate mediated by ASIC, P2X, and TRPV1. AU - Light,Alan R, AU - Hughen,Ronald W, AU - Zhang,Jie, AU - Rainier,Jon, AU - Liu,Zhuqing, AU - Lee,Jeewoo, Y1 - 2008/05/28/ PY - 2008/5/30/pubmed PY - 2008/12/17/medline PY - 2008/5/30/entrez SP - 1184 EP - 201 JF - Journal of neurophysiology JO - J Neurophysiol VL - 100 IS - 3 N2 - The adequate stimuli and molecular receptors for muscle metaboreceptors and nociceptors are still under investigation. We used calcium imaging of cultured primary sensory dorsal root ganglion (DRG) neurons from C57Bl/6 mice to determine candidates for metabolites that could be the adequate stimuli and receptors that could detect these stimuli. Retrograde DiI labeling determined that some of these neurons innervated skeletal muscle. We found that combinations of protons, ATP, and lactate were much more effective than individually applied compounds for activating rapid calcium increases in muscle-innervating dorsal root ganglion neurons. Antagonists for P2X, ASIC, and TRPV1 receptors suggested that these three receptors act together to detect protons, ATP, and lactate when presented together in physiologically relevant concentrations. Two populations of muscle-innervating DRG neurons were found. One responded to low metabolite levels (likely nonnoxious) and used ASIC3, P2X5, and TRPV1 as molecular receptors to detect these metabolites. The other responded to high levels of metabolites (likely noxious) and used ASIC3, P2X4, and TRPV1 as their molecular receptors. We conclude that a combination of ASIC, P2X5 and/or P2X4, and TRPV1 are the molecular receptors used to detect metabolites by muscle-innervating sensory neurons. We further conclude that the adequate stimuli for muscle metaboreceptors and nociceptors are combinations of protons, ATP, and lactate. SN - 0022-3077 UR - https://www.unboundmedicine.com/medline/citation/18509077/Dorsal_root_ganglion_neurons_innervating_skeletal_muscle_respond_to_physiological_combinations_of_protons_ATP_and_lactate_mediated_by_ASIC_P2X_and_TRPV1_ L2 - https://journals.physiology.org/doi/10.1152/jn.01344.2007?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -