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. 1996 Sep;119(1):81–90. doi: 10.1111/j.1476-5381.1996.tb15680.x

Effect of capsaicin and analogues on potassium and calcium currents and vanilloid receptors in Xenopus embryo spinal neurones.

F M Kuenzi 1, N Dale 1
PMCID: PMC1915739  PMID: 8872360

Abstract

1. The potassium current in embryo spinal neurones of Xenopus consists of at least two kinetically distinct components with overlapping voltage-dependencies of activation. We investigated whether capsaicin might specifically block these components in acutely dissociated neurones from stage 37/38 embryos by use of standard patch clamp techniques. 2. Capsaicin caused a time-dependent block of both the slow and fast components of the potassium current. The concentration-dependence was described by the Hill equation with a KD of 21 microM and a coefficient of 1.5 (n = 9-11 at each concentration). Differences between the observed and fitted values were not significant at the 5% level (chi(2) = 2.80, 6 degrees of freedom). 3. Capsaicin did not affect the time course or voltage-sensitivity of activation, but the steady-state block was voltage-dependent. The block could be relieved by hyperpolarization, and the rate of the removal of block was voltage- and time-dependent. The time constant for the blocking reaction was also voltage-dependent for voltage steps below +30 mV, but above this level it was voltage-independent. These results suggest that capsaicin blocks potassium channels by an open channel mechanism. 4. Other derivatives of vanillin, such as capsazepine, resiniferatoxin, and piperine also blocked potassium channels. Capsazepine and resiniferatoxin caused a greater block than similar concentrations of capsaicin, and in the case of capsazepine, the block was also clearly time-dependent. 5. Capsaicin and capsazepine also blocked calcium currents in a time-dependent manner. Fitting the Hill equation to the averaged data gave a KD of 43.5 microM, and a coefficient of 1.35 (n = 11 at each concentration). The fitted values were not significantly different from the observed means at the 5% level (chi(2) = 12.1, 6 degrees of freedom). 6. Six out of 29 Rohon-Beard sensory neurones responded to capsaicin with an inward current that appeared to be similar to the capsaicin activation of mammalian C sensory neurones. This response saturated at 10 microM capsaicin.

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Selected References

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  1. Akerman K. E., Grönblad M. Intracellular free [Ca2+] and [Na+] in response to capsaicin in cultured dorsal root ganglion cells. Neurosci Lett. 1992 Nov 23;147(1):13–15. doi: 10.1016/0304-3940(92)90763-w. [DOI] [PubMed] [Google Scholar]
  2. Akins P. T., McCleskey E. W. Characterization of potassium currents in adult rat sensory neurons and modulation by opioids and cyclic AMP. Neuroscience. 1993 Oct;56(3):759–769. doi: 10.1016/0306-4522(93)90372-m. [DOI] [PubMed] [Google Scholar]
  3. Armstrong C. M. Inactivation of the potassium conductance and related phenomena caused by quaternary ammonium ion injection in squid axons. J Gen Physiol. 1969 Nov;54(5):553–575. doi: 10.1085/jgp.54.5.553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baker M. D., Ritchie J. M. The action of capsaicin on type I delayed rectifier K+ currents in rabbit Schwann cells. Proc Biol Sci. 1994 Mar 22;255(1344):259–265. doi: 10.1098/rspb.1994.0037. [DOI] [PubMed] [Google Scholar]
  5. Bevan S., Hothi S., Hughes G., James I. F., Rang H. P., Shah K., Walpole C. S., Yeats J. C. Capsazepine: a competitive antagonist of the sensory neurone excitant capsaicin. Br J Pharmacol. 1992 Oct;107(2):544–552. doi: 10.1111/j.1476-5381.1992.tb12781.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bleakman D., Brorson J. R., Miller R. J. The effect of capsaicin on voltage-gated calcium currents and calcium signals in cultured dorsal root ganglion cells. Br J Pharmacol. 1990 Oct;101(2):423–431. doi: 10.1111/j.1476-5381.1990.tb12725.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Castle N. A. Differential inhibition of potassium currents in rat ventricular myocytes by capsaicin. Cardiovasc Res. 1992 Nov;26(11):1137–1144. doi: 10.1093/cvr/26.11.1137. [DOI] [PubMed] [Google Scholar]
  8. Clarke J. D., Hayes B. P., Hunt S. P., Roberts A. Sensory physiology, anatomy and immunohistochemistry of Rohon-Beard neurones in embryos of Xenopus laevis. J Physiol. 1984 Mar;348:511–525. doi: 10.1113/jphysiol.1984.sp015122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dale N. A large, sustained Na(+)- and voltage-dependent K+ current in spinal neurons of the frog embryo. J Physiol. 1993 Mar;462:349–372. doi: 10.1113/jphysiol.1993.sp019559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dale N. Kinetic characterization of the voltage-gated currents possessed by Xenopus embryo spinal neurons. J Physiol. 1995 Dec 1;489(Pt 2):473–488. doi: 10.1113/jphysiol.1995.sp021066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dale Nicholas. The Isolation and Identification of Spinal Neurons That Control Movement in the Xenopus Embryo. Eur J Neurosci. 1991;3(10):1025–1035. doi: 10.1111/j.1460-9568.1991.tb00039.x. [DOI] [PubMed] [Google Scholar]
  12. Docherty R. J., Robertson B., Bevan S. Capsaicin causes prolonged inhibition of voltage-activated calcium currents in adult rat dorsal root ganglion neurons in culture. Neuroscience. 1991;40(2):513–521. doi: 10.1016/0306-4522(91)90137-d. [DOI] [PubMed] [Google Scholar]
  13. Dubois J. M. Capsaicin blocks one class of K+ channels in the frog node of Ranvier. Brain Res. 1982 Aug 12;245(2):372–375. doi: 10.1016/0006-8993(82)90820-4. [DOI] [PubMed] [Google Scholar]
  14. Grissmer S., Nguyen A. N., Aiyar J., Hanson D. C., Mather R. J., Gutman G. A., Karmilowicz M. J., Auperin D. D., Chandy K. G. Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines. Mol Pharmacol. 1994 Jun;45(6):1227–1234. [PubMed] [Google Scholar]
  15. HODGKIN A. L., HUXLEY A. F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol. 1952 Aug;117(4):500–544. doi: 10.1113/jphysiol.1952.sp004764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hoshi T., Zagotta W. N., Aldrich R. W. Two types of inactivation in Shaker K+ channels: effects of alterations in the carboxy-terminal region. Neuron. 1991 Oct;7(4):547–556. doi: 10.1016/0896-6273(91)90367-9. [DOI] [PubMed] [Google Scholar]
  17. Janusz J. M., Buckwalter B. L., Young P. A., LaHann T. R., Farmer R. W., Kasting G. B., Loomans M. E., Kerckaert G. A., Maddin C. S., Berman E. F. Vanilloids. 1. Analogs of capsaicin with antinociceptive and antiinflammatory activity. J Med Chem. 1993 Sep 3;36(18):2595–2604. doi: 10.1021/jm00070a002. [DOI] [PubMed] [Google Scholar]
  18. Kehl S. J. Block by capsaicin of voltage-gated K+ currents in melanotrophs of the rat pituitary. Br J Pharmacol. 1994 Jun;112(2):616–624. doi: 10.1111/j.1476-5381.1994.tb13119.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kusano K., Gainer H. Modulation of voltage-activated Ca currents by pain-inducing agents in a dorsal root ganglion neuronal line, F-11. J Neurosci Res. 1993 Feb 1;34(2):158–169. doi: 10.1002/jnr.490340203. [DOI] [PubMed] [Google Scholar]
  20. Lee K. S., Tsien R. W. Mechanism of calcium channel blockade by verapamil, D600, diltiazem and nitrendipine in single dialysed heart cells. Nature. 1983 Apr 28;302(5911):790–794. doi: 10.1038/302790a0. [DOI] [PubMed] [Google Scholar]
  21. Marsh S. J., Stansfeld C. E., Brown D. A., Davey R., McCarthy D. The mechanism of action of capsaicin on sensory C-type neurons and their axons in vitro. Neuroscience. 1987 Oct;23(1):275–289. doi: 10.1016/0306-4522(87)90289-2. [DOI] [PubMed] [Google Scholar]
  22. Petersen M., Pierau F. K., Weyrich M. The influence of capsaicin on membrane currents in dorsal root ganglion neurones of guinea-pig and chicken. Pflugers Arch. 1987 Aug;409(4-5):403–410. doi: 10.1007/BF00583794. [DOI] [PubMed] [Google Scholar]
  23. Petersen M., Wagner G., Pierau F. K. Modulation of calcium-currents by capsaicin in a subpopulation of sensory neurones of guinea pig. Naunyn Schmiedebergs Arch Pharmacol. 1989 Jan-Feb;339(1-2):184–191. doi: 10.1007/BF00165142. [DOI] [PubMed] [Google Scholar]
  24. Rampe D., Wible B., Fedida D., Dage R. C., Brown A. M. Verapamil blocks a rapidly activating delayed rectifier K+ channel cloned from human heart. Mol Pharmacol. 1993 Sep;44(3):642–648. [PubMed] [Google Scholar]
  25. Szallasi A., Blumberg P. M. Resiniferatoxin, a phorbol-related diterpene, acts as an ultrapotent analog of capsaicin, the irritant constituent in red pepper. Neuroscience. 1989;30(2):515–520. doi: 10.1016/0306-4522(89)90269-8. [DOI] [PubMed] [Google Scholar]
  26. Urban L., Dray A. Actions of capsaicin on mouse dorsal root ganglion cells in vitro. Neurosci Lett. 1993 Jul 23;157(2):187–190. doi: 10.1016/0304-3940(93)90733-2. [DOI] [PubMed] [Google Scholar]
  27. Wall M. J., Dale N. A role for potassium currents in the generation of the swimming motor pattern of Xenopus embryos. J Neurophysiol. 1994 Jul;72(1):337–348. doi: 10.1152/jn.1994.72.1.337. [DOI] [PubMed] [Google Scholar]
  28. Wall M. J., Dale N. A slowly activating Ca(2+)-dependent K+ current that plays a role in termination of swimming in Xenopus embryos. J Physiol. 1995 Sep 15;487(Pt 3):557–572. doi: 10.1113/jphysiol.1995.sp020900. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Walpole C. S., Bevan S., Bovermann G., Boelsterli J. J., Breckenridge R., Davies J. W., Hughes G. A., James I., Oberer L., Winter J. The discovery of capsazepine, the first competitive antagonist of the sensory neuron excitants capsaicin and resiniferatoxin. J Med Chem. 1994 Jun 24;37(13):1942–1954. doi: 10.1021/jm00039a006. [DOI] [PubMed] [Google Scholar]
  30. Winter J., Dray A., Wood J. N., Yeats J. C., Bevan S. Cellular mechanism of action of resiniferatoxin: a potent sensory neuron excitotoxin. Brain Res. 1990 Jun 18;520(1-2):131–140. doi: 10.1016/0006-8993(90)91698-g. [DOI] [PubMed] [Google Scholar]
  31. Wood J. N., Winter J., James I. F., Rang H. P., Yeats J., Bevan S. Capsaicin-induced ion fluxes in dorsal root ganglion cells in culture. J Neurosci. 1988 Sep;8(9):3208–3220. doi: 10.1523/JNEUROSCI.08-09-03208.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Zhang J. F., Ellinor P. T., Aldrich R. W., Tsien R. W. Molecular determinants of voltage-dependent inactivation in calcium channels. Nature. 1994 Nov 3;372(6501):97–100. doi: 10.1038/372097a0. [DOI] [PubMed] [Google Scholar]

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