Differential effects of capsaicin on rat visceral sensory neurons.
Nodose neurons play an important role in the regulation of visceral function. Recent studies demonstrated that about 80% of these neurons contain messenger RNA for the capsaicin receptor, a heat-sensitive ion channel. Nodose neurons express voltage-sensitive sodium currents that can be differentiated based on their sensitivity to tetrodotoxin. Considering the potential role of tetrodotoxin-resistant sodium currents in somatosensory neurons, sodium channel expression and sodium currents were studied in nodose neurons. The results were correlated with the response to capsaicin. Nodose neurons contain messenger RNA for the tetrodotoxin-resistant sodium channel PN3. Consistent with these findings, about half of the neurons predominantly expressed tetrodotoxin-resistant sodium currents. In 54% (47/87) of the cells, capsaicin triggered an increase in intracellular calcium. Similarly, in 42% (18/43) of the cells, capsaicin elicited an inward current. There was no relationship between cell size (r=0.07) or sodium current properties (r=0.14) and the response to capsaicin. Micromolar concentrations of capsaicin inhibited voltage-dependent sodium, calcium and potassium currents. This effect was use dependent and did not involve the capsaicin receptor. In conclusion, capsaicin changed the excitability of visceral sensory neurons by blocking voltage-dependent ion channels, an effect that may contribute to the analgesic properties of capsaicin.
Bielefeldt
K
K
Department of Internal Medicine, Division of Gastroenterology, University of Iowa, 4614 JCP, 200 Hawkins Drive, Iowa City, IA 52242, USA. Klaus-Bielefeldt@mail.int-med.uiowa.edu
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002478:Cells, Cultured; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009619:Nociceptors / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009620:Nodose Ganglion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D020033:Protein Isoforms / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000187:drug effects* / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D050916:TRPV Cation Channels; D013779:Tetrodotoxin / Q000494:pharmacology; D017833:Visceral Afferents / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D015221:Potassium Channels; D020033:Protein Isoforms; D011955:Receptors, Drug; D015222:Sodium Channels; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D013779:Tetrodotoxin; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium