Proinflammatory mediators, stimulators of sensory neuron excitability via the expression of acid-sensing ion channels.
Tissue acidosis is an important feature of inflammation. It is a direct cause of pain and hyperalgesia. Protons activate sensory neurons mainly through acid-sensing ion channels (ASICs) and the subsequent membrane depolarization that leads to action potential generation. We had previously shown that ASIC transcript levels were increased in inflammatory conditions in vivo. We have now found that this increase is caused by the proinflammatory mediators NGF, serotonin, interleukin-1, and bradykinin. A mixture of these mediators increases ASIC-like current amplitude on sensory neurons as well as the number of ASIC-expressing neurons and leads to a higher sensory neuron excitability. An analysis of the promoter region of the ASIC3 encoding gene, an ASIC specifically expressed in sensory neurons and associated with chest pain that accompanies cardiac ischemia, reveals that gene transcription is controlled by NGF and serotonin.
Mamet
Julien
J
Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique-Unité Mixte de Recherche 6097, Sophia Antipolis, 06560 Valbonne, France.
Baron
Anne
A
Lazdunski
Michel
M
Voilley
Nicolas
N
D062565:Acid Sensing Ion Channels; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002478:Cells, Cultured; D004553:Electric Conductivity; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D018836:Inflammation Mediators / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D015640:Ion Channel Gating; D008565:Membrane Proteins; D020932:Nerve Growth Factor / Q000494:pharmacology; D009419:Nerve Tissue Proteins; D009475:Neurons, Afferent / Q000378:metabolism* / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D015222:Sodium Channels / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D015533:Transcriptional Activation
C112231:ASIC3 protein, human; C568269:ASIC3 protein, rat; D062565:Acid Sensing Ion Channels; D018836:Inflammation Mediators; D007375:Interleukin-1; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D015222:Sodium Channels; D012701:Serotonin; D020932:Nerve Growth Factor; D001920:Bradykinin