Petersen M, Lamotte R H, Klusch A, Kniffki K D
Department of Physiology, Julius Maximilian University Würzburg, Germany.
Neuroscience. 1996 Nov;75(2):495-505. doi: 10.1016/0306-4522(96)00259-x.
The response to capsaicin in functional assays suggests multiple sites of capsaicin action. This hypothesis is supported by the results of the present patch-clamp study of isolated dorsal root ganglion cells of the rat. The response to a prolonged application of capsaicin of different concentrations in an external solution with different ion compositions was investigated. Capsaicin evoked up to three distinct current components. The first and second current components could be activated independently. The third component occurred only in the presence of sodium and only in cells in which the second component was also elicited. In an extracellular solution with a physiological composition of ions and 300 nM capsaicin, the peaks of the three components, when evoked, occurred at 10.1 +/- 1.35 s (mean +/- S.E.M., n = 9), 44.0 +/- 2.64 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 capsaicin. A low concentration predominantly elicited the second component, while a high concentration activated the first and suppressed the second one. The third component seems to be a secondary response of the cell and was not investigated in detail. The activation and decay phases of the first two current components could be fitted by single exponential functions, whereas those of the third component could not. The first and second current components were carried by sodium and calcium. After tachyphylaxis, if the extracellular medium was then acidified to a pH of 6.3, the second component alone could then be elicited by capsaicin. The results demonstrate that capsaicin can elicit different current components that are distinguishable by their time-course, by the effects of acidification of the extracellular solution and by the concentration of capsaicin required to activate these currents. We postulate two distinct binding sites of capsaicin causing two distinct current components. This may account for the variety of physiological responses evoked by capsaicin and the variations in these responses between species.
功能试验中对辣椒素的反应表明辣椒素存在多个作用位点。本项对大鼠离体背根神经节细胞进行的膜片钳研究结果支持了这一假说。研究了在具有不同离子组成的外部溶液中长时间施加不同浓度辣椒素时的反应。辣椒素可诱发多达三种不同的电流成分。第一和第二电流成分可独立激活。第三成分仅在有钠存在时出现，且仅在能诱发第二成分的细胞中出现。在具有生理离子组成且含300 nM辣椒素的细胞外溶液中，诱发时三种成分的峰值分别出现在10.1±1.35秒（平均值±标准误，n = 9）、44.0±2.64秒（n = 16）和79.0±8.10秒（n = 5）。第一和/或第二电流成分的激活取决于辣椒素的浓度。低浓度主要诱发第二成分，而高浓度则激活第一成分并抑制第二成分。第三成分似乎是细胞的继发反应，未作详细研究。前两个电流成分的激活和衰减阶段可用单指数函数拟合，而第三成分则不能。第一和第二电流成分由钠和钙携带。脱敏后，如果将细胞外介质酸化至pH 6.3，辣椒素随后只能诱发第二成分。结果表明，辣椒素可诱发不同的电流成分，这些成分可通过其时程、细胞外溶液酸化的影响以及激活这些电流所需的辣椒素浓度加以区分。我们推测辣椒素存在两个不同的结合位点，导致两种不同的电流成分。这可能解释了辣椒素诱发的多种生理反应以及不同物种间这些反应的差异。
