Inhibitory effects of capsaicin on voltage-gated potassium channels by TRPV1-independent pathway.
Inhibitory effects of capsaicin on voltage-gated potassium channels by TRPV1-independent pathway.
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DOI：
10.1007/s10571-014-0041-1
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发表时间：
2014-05
影响因子：
4
通讯作者：
Liu, Lieju
中科院分区：
文献类型：
--
作者：
Yang, Rong;Xiong, Zhe;Liu, Changjin;Liu, Lieju
我们在大鼠三叉神经节（TG）观察到瞬时受体电位香草酸1（TRPV 1）受体激活剂辣椒素（capsaicin）对辣椒素敏感（CS）和辣椒素不敏感（CIS）神经元的瞬时钾电流（IA）有抑制作用。这表明辣椒素对IA的抑制作用有两种不同的机制：TRPV 1依赖性途径和TRPV 1非依赖性途径。本研究的主要目的是进一步研究辣椒素对电压门控钾通道（VGPCs）的TRPV 1非依赖性作用。用全细胞膜片钳技术记录培养的TRPV 1基因敲除（TRPV 1 −/−）小鼠TG神经元的IA和持续钾电流（IK）。我们发现，辣椒素可逆地抑制IA和IK的剂量依赖性的方式。辣椒素（30 µM）没有改变IA和IK的激活曲线，但将失活电压曲线移至超极化方向，从而增加静息电位下失活的VGPC数量。高浓度辣椒素对IK和IA无使用依赖性阻滞，恢复时间延迟。此外，forskolin，腺苷酸环化酶激动剂，选择性地降低由辣椒素IK的抑制作用，而没有影响IA的抑制。这些结果表明辣椒素通过TRPV 1非依赖性和PKA依赖性机制抑制VGPCs，这可能与辣椒素诱导的伤害性感受有关。
Previously we observed that capsaicin, a transient receptor potential vanilloid 1 (TRPV1) receptor activator, inhibited transient potassium current (IA) in capsaicin-sensitive (CS) and capsaicin-insensitive (CIS) trigeminal ganglion (TG) neurons from rats. It suggested that the inhibitory effects of capsaicin on IA have two different mechanisms: TRPV1-dependent and TRPV1-independent pathways. The main purpose of this study is to further investigate the TRPV1 independent effects of capsaicin on voltage-gated potassium channels (VGPCs). Whole cell patch clamp technique was used to record IA and sustained potassium current (IK) in cultured TG neurons from trpv1 knockout (TRPV1−/−) mice. We found that capsaicin reversibly inhibited IA and IK in a dose-dependent manner. Capsaicin (30 µM) did not alter the activation curve of IA and IK but shifted the inactivation-voltage curve to hyperpolarizing direction, thereby increasing the number of inactivated VGPCs at the resting potential. Administration of high concentrations capsaicin, no use-dependent block and delay of recovery time course were found on IK and IA. Moreover, forskolin, an adenylate cyclase agonist, selectively decreased the inhibitory effects of IK by capsaicin, whereas no influenced the inhibitions of IA. These results suggest that capsaicin inhibits the VGPCs through TRPV1-independent and PKA-dependent mechanisms, which may contribute to the capsaicin-induced nociception.
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影响因子：
6.1
作者：
Premkumar LS;Abooj M
通讯作者：
Abooj M
DOI：
10.1165/rcmb.2010-0332oc
发表时间：
2011-10-01
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作者：
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