Capsaicin-induced currents with distinct desensitization and Ca2+ dependence in rat trigeminal ganglion cells.
1. Whole cell patch-clamp records from cultured rat trigeminal ganglion cells having soma diameters ranging from 20 to 50 microM revealed that capsaicin activated two inward currents and an outward current. At -60 mV, the inward currents could be distinguished by their different peak times, which were 4.2 +/- 3.1 and 41.4 +/- 16.4 (SD) s. 2. Cells with the smallest soma diameters had the largest current densities. 3. The more rapidly activating current had a linear current-voltage relation and a reversal potential near 0 mV. 4. The more slowly activating current is not a Ca(2+)-activated Cl- current. 5. The peak of the rapid current (Ip)-capsaicin concentration (C) relationship was characterized by Ip/Ipmax = [1 + (C/Kd)n]-1, where n = 1.2 and the dissociation constant (Kd) = 0.68 microM. 6. The rapidly activating current was heterogeneous in regards to both its rate of activation and extent of desensitization. In cells bathed in buffer containing calcium and held at -60 mV, most of the capsaicin-activated currents desensitized. Removal of extracellular Ca2+ could reduce, eliminate, or have no effect on desensitization. 7. At positive holding potentials the currents very slowly desensitized, even in the presence of Ca2+. 8. Repeated 30-s applications of 1 microM capsaicin separated by 0.5, 2.5, and 5.5 min all induced tachyphylaxis. Tachyphylaxis decreased exponentially until the current remained approximately constant. Decreasing the time between capsaicin applications increased the extent of tachyphylaxis, whereas elimination of extracellular Ca2+ markedly reduced tachyphylaxis.
Liu
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Department of Neurobiology and Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
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D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D002211:Capsaicin / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D004553:Electric Conductivity; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000378:metabolism; D013618:Tachyphylaxis / Q000502:physiology; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects*
D015220:Calcium Channels; D011955:Receptors, Drug; D002211:Capsaicin