Department of Cell Physiology, Ruhr-University-Bochum Bochum, Germany.
Front Pharmacol. 2013 Nov 18;4:141. doi: 10.3389/fphar.2013.00141. eCollection 2013.
For a long time, the focus of trigeminal chemoperception has rested almost exclusively on TRP channels. However, two-pore domain (K2P) potassium channels have recently been identified as targets for substances associated with typical trigeminal sensations, such as numbing and tingling. In addition, they have been shown to be modulated by several TRP agonists. We investigated whether the pungent substances piperine, capsaicin, 6-gingerol and polygodial have an effect on human K2P channels. For this purpose, we evaluated the effects of these pungent substances on both wild-type and mutant K2P channels by means of two-electrode voltage-clamp experiments using Xenopus laevis oocytes. All four pungent substances were found to inhibit the basal activity of TASK-1 (K2P 3.1), TASK-3 (K2P 9.1), and TRESK (K2P 18.1) channels. This inhibitory effect was dose-dependent and, with the exception of polygodial on TASK-1, fully reversible. However, only piperine exhibited an IC50 similar to its reported EC50 on TRP channels. Finally, we observed for TASK-3 that mutating H98 to E markedly decreased the inhibition induced by piperine, capsaicin, and 6-gingerol, but not by polygodial. Our data contribute to the relatively sparse knowledge concerning the pharmacology of K2P channels and also raise the question of whether K2P channels could be involved in the pungency perception of piperine.
长期以来，三叉神经化学感受的焦点几乎完全集中在 TRP 通道上。然而，最近发现双孔域（K2P）钾通道是与典型三叉神经感觉相关的物质的靶点，如麻木和刺痛。此外，它们已被证明可被几种 TRP 激动剂调节。我们研究了辛辣物质胡椒碱、辣椒素、6-姜酚和博落回碱是否对人类 K2P 通道有影响。为此，我们通过使用非洲爪蟾卵母细胞的双电极电压钳实验评估了这些辛辣物质对野生型和突变型 K2P 通道的影响。发现这四种辛辣物质均抑制 TASK-1（K2P 3.1）、TASK-3（K2P 9.1）和 TRESK（K2P 18.1）通道的基础活性。这种抑制作用呈剂量依赖性，除了博落回碱对 TASK-1 的作用外，完全是可逆的。然而，只有胡椒碱表现出与其在 TRP 通道上报道的 EC50 相似的 IC50。最后，我们观察到 TASK-3 中的 H98 突变为 E 可显著降低胡椒碱、辣椒素和 6-姜酚诱导的抑制作用，但对博落回碱没有影响。我们的数据有助于了解 K2P 通道的药理学，也提出了 K2P 通道是否可能参与胡椒碱的辣味感知的问题。
