Dorsal Root Ganglion Neurons Innervating Skeletal Muscle Respond to Physiological Combinations of Protons, ATP, and Lactate Mediated by ASIC, P2X, and TRPV1 Export

@article{citeulike:3441619, 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. 10.1152/jn.01344.2007}, author = {Light, Alan R. and Hughen, Ronald W. and Zhang, Jie and Rainier, Jon and Liu, Zhuqing and Lee, Jeewoo}, citeulike-article-id = {3441619}, citeulike-linkout-0 = {http://dx.doi.org/10.1152/jn.01344.2007}, citeulike-linkout-1 = {http://jn.physiology.org/cgi/content/abstract/100/3/1184}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18509077}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18509077}, day = {1}, doi = {10.1152/jn.01344.2007}, journal = {J Neurophysiol}, keywords = {asic, atp, drg, lactate, muscle, p2x, trpv1}, month = {September}, number = {3}, pages = {1184--1201}, posted-at = {2008-10-23 02:45:06}, priority = {3}, title = {Dorsal Root Ganglion Neurons Innervating Skeletal Muscle Respond to Physiological Combinations of Protons, ATP, and Lactate Mediated by ASIC, P2X, and TRPV1}, url = {http://dx.doi.org/10.1152/jn.01344.2007}, volume = {100}, year = {2008} }

TY - JOUR ID - citeulike:3441619 L3 - citeulike-article-id:3441619 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. 10.1152/jn.01344.2007 IS - 3 JF - J Neurophysiol EP - 1201 TI - Dorsal Root Ganglion Neurons Innervating Skeletal Muscle Respond to Physiological Combinations of Protons, ATP, and Lactate Mediated by ASIC, P2X, and TRPV1 VL - 100 SP - 1184 KW - asic KW - atp KW - drg KW - lactate KW - muscle KW - p2x KW - trpv1 AU - Light, Alan AU - Hughen, Ronald AU - Zhang, Jie AU - Rainier, Jon AU - Liu, Zhuqing AU - Lee, Jeewoo PY - 2008/09/01/ UR - http://dx.doi.org/10.1152/jn.01344.2007 ER -