Capsaicin sensitivity and voltage-gated sodium currents in colon sensory neurons from rat dorsal root ganglia.
DiI-labeled colon sensory neurons were acutely dissociated from S1 rat dorsal root ganglia (DRG) and studied using perforated whole cell patch-clamp techniques. Forty-six percent (54/116) of labeled sensory neurons responded to capsaicin (10(-8)- 10(-5) M) with an increase in inward current, which was a nonspecific cation conductance. Responses to capsaicin applied by puffer ejection were dependent on dose, with a half-maximal response at 4.9 x 10(-7) M; bath application was characterized by marked desensitization. Voltage-gated Na(+) currents in 23 of 30 DRG cells exhibited both TTX-sensitive and TTX-resistant components. In these cells, capsaicin induced an inward current in 11 of 17 cells tested. Of the cells containing only a TTX-sensitive component, none of six cells tested was sensitive to capsaicin. In all cells that responded to capsaicin with an increase in inward current, capsaicin abolished voltage-gated Na(+) currents (n = 21). Capsazepine (10(-6) M) significantly attenuated both the increase in inward current and the reduction in Na(+) currents. Na(+) currents were not significantly altered by adenosine, bradykinin, histamine, PGE(2), or serotonin at 10(-6) M and 10(-5) M. These findings may have important implications for understanding both the irritant and analgesic properties of capsaicin.
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Department of Pharmacology, College of Medicine, University of Iowa, Iowa City 52242, Iowa. xin-su@uiowa.edu
Wachtel
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Gebhart
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D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000241:Adenosine / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D002232:Carbocyanines; D003106:Colon / Q000294:innervation*; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005456:Fluorescent Dyes; D005727:Ganglia, Spinal / Q000166:cytology* / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009475:Neurons, Afferent / Q000737:chemistry / Q000187:drug effects*; D010146:Pain / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D000700:Analgesics; C101089:CM-DiI; D002232:Carbocyanines; D005456:Fluorescent Dyes; D015222:Sodium Channels; D012701:Serotonin; D013779:Tetrodotoxin; D006632:Histamine; D012964:Sodium; D000241:Adenosine; D015232:Dinoprostone; D002211:Capsaicin; D001920:Bradykinin