MULTIPLE CAPSAICIN-EVOKED CURRENTS IN ISOLATED RAT SENSORY NEURONS

The response to capsaicin in functional assays suggests multiple sites of capsaicin action. This hypothesis is supported by the results of t he present patch-clamp study of isolated dorsal root ganglion cells of the rat. The response to a prolonged application of capsaicin of diff erent concentrations in an external solution with different ion compos itions was investigated. Capsaicin evoked up to three distinct current components. The first and second current components could be activate d independently. The third component occurred only in the presence of sodium and only in cells in which the second component was also elicit ed. In an extracellular solution with a physiological composition of i ons and 300 nM capsaicin, the peaks of the three components, when evok ed, occurred at 10.1 +/- 1.35 s (mean +/- S.E.M., n = 9), 44.0 +/- 2.6 4 s (n = 16) and 79.0 +/- 8.10 s (n = 5). The activation of the first and/or second current component depended on the concentration of capsa icin. A low concentration predominantly elicited the second component, while a high concentration activated the first and suppressed the sec ond one. The third component seems to be a secondary response of the c ell and was not investigated in detail. The activation and decay phase s of the first two current components could be fitted by single expone ntial functions, whereas those of the third component could not. The f irst and second current components were carried by sodium and calcium. After tachyphylaxis, ii the extracellular medium was then acidified t o a pH of 6.3, the second component alone could then be elicited by ca psaicin. The results demonstrate that capsaicin can elicit different c urrent components that are distinguishable by their time-course, by th e effects of acidification of the extracellular solution and by the co ncentration of capsaicin required to activate these currents. We postu late two distinct binding sites of capsaicin causing two distinct curr ent components. This may account for the variety of physiological resp onses evoked by capsaicin and the variations in these responses betwee n species. Copyright (C) 1996 IBRO.