Hagenacker Tim, Splettstoesser Frank, Greffrath Wolfgang, Treede Rolf-Detlef, Büsselberg Dietrich
Institut für Physiologie, Universitätsklinikum Essen, Universität Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany.
Brain Res. 2005 Nov 16;1062(1-2):74-85. doi: 10.1016/j.brainres.2005.09.033. Epub 2005 Nov 2.
It is discussed whether capsaicin, an agonist of the pain mediating TRPV1 receptor, decreases or increases voltage-activated calcium channel (VACC) currents (I(Ca(V))). I(Ca(V)) were isolated in cultured dorsal root ganglion (DRG) neurones of rats using the whole cell patch clamp method and Ba2+ as charge carrier. In large diameter neurones (>35 micorm), a concentration of 50 microM was needed to reduce I(Ca(V)) (activated by depolarizations to 0 mV) by 80%, while in small diameter neurones (< or =30 microm), the IC50 was 0.36 microM. This effect was concentration dependent with a threshold below 0.025 microM and maximal blockade (>80%) at 5 microM. The current-voltage relation was shifted to the hyperpolarized direction with an increase of the current between -40 and -10 mV and a decrease between 0 and +50 mV. Isolation of L-, N-, and T-type calcium channels resulted in differential effects when 0.1 microM capsaicin was applied. While T-type channel currents were equally reduced over the voltage range, L-type channel currents were additionally shifted to the hyperpolarized direction by 10 to 20 mV. N-type channel currents expressed either a shift (3 cells) or a reduction of the current (4 cells) or both (3 cells). Thus, capsaicin increases I(Ca(V)) at negative and decreases I(Ca(V)) at positive voltages by differentially affecting L-, N-, and T-type calcium channels. These effects of capsaicin on different VACCs in small DRG neurones, which most likely express the TRPV1 receptor, may represent another mechanism of action of the pungent substance capsaicin in addition to opening of TRPV1.
人们探讨了辣椒素（一种介导疼痛的TRPV1受体激动剂）是会降低还是增加电压激活钙通道（VACC）电流（I(Ca(V))）。采用全细胞膜片钳技术，以Ba2+作为电荷载体，在大鼠背根神经节（DRG）神经元培养物中分离出I(Ca(V))。在大直径神经元（>35微米）中，需要50微摩尔的浓度才能将I(Ca(V))（由去极化至0毫伏激活）降低80%，而在小直径神经元（≤30微米）中，半数抑制浓度（IC50）为0.36微摩尔。这种效应呈浓度依赖性，阈值低于0.025微摩尔，在5微摩尔时达到最大阻断（>80%）。电流-电压关系向超极化方向移动，在-40至-10毫伏之间电流增加，在0至+50毫伏之间电流降低。当应用0.1微摩尔辣椒素时，分离L型、N型和T型钙通道会产生不同的效应。虽然T型通道电流在整个电压范围内均被同等程度地降低，但L型通道电流还额外向超极化方向移动了10至20毫伏。N型通道电流要么出现电流偏移（3个细胞），要么出现电流降低（4个细胞），要么两者都有（3个细胞）。因此，辣椒素通过对L型、N型和T型钙通道的不同影响，在负电压时增加I(Ca(V))，在正电压时降低I(Ca(V))。辣椒素对小DRG神经元中不同VACC的这些作用，很可能表达TRPV1受体，这可能是除了打开TRPV1之外，这种辛辣物质辣椒素的另一种作用机制。
