Structural determinant of TRPV1 desensitization interacts with calmodulin
Structural determinant of TRPV1 desensitization interacts with calmodulin
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DOI：
10.1073/pnas.1337252100
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发表时间：
2003-06-24
影响因子：
11.1
通讯作者：
Tominaga, M
中科院分区：
文献类型：
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作者：
Numazaki, M;Tominaga, T;Tominaga, M
辣椒素受体TRPV1 （VR1）是一种感觉神经元特异性离子通道，作为产生疼痛的化学和物理刺激的多模态检测器。在膜片钳实验中观察到，当使用异种表达系统和天然感觉神经节时，细胞外Ca2+依赖性TRPV1脱敏被认为是辣椒素作为镇痛疗法的矛盾效果的一种机制。在这里，我们发现Ca2+结合蛋白钙调蛋白与TRPV1 C端35-aa片段结合，钙调蛋白结合片段的破坏阻止了TRPV1的脱敏。因此，干扰35-aa片段的化合物可能对治疗疼痛有用。
The capsaicin receptor, TRPV1 (VR1), is a sensory neuron-specific ion channel that serves as a polymodal detector of pain-producing chemical and physical stimuli. Extracellular Ca2+-dependent desensitization of TRPV1 observed in patch-clamp experiments when using both heterologous expression systems and native sensory ganglia is thought to be one mechanism underlying the paradoxical effectiveness of capsaicin as an analgesic therapy. Here, we show that the Ca2+-binding protein calmodulin binds to a 35-aa segment in the C terminus of TRPV1, and that disruption of the calmodulin-binding segment prevents TRPV1 desensitization. Compounds that interfere with the 35-aa segment could therefore prove useful in the treatment of pain.