Transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel, is mainly expressed in nociceptive primary sensory neurons. Sensitivity of TRPV1 to several stimuli is known to vary among species, specifically, the avian orthologue is nearly insensitive to capsaicin. Extracellular sodium ions ([Na⁺]_o) regulate TRPV1 activity in mammals, but their regulatory role on chicken TRPV1 (cTRPV1) is unknown. Here, we focused on the actions of capsaicin and low [Na⁺]_o on cTRPV1 activity. In chicken dorsal root ganglion (cDRG) neurons, capsaicin elicited [Ca²⁺]_i increases, but its effective concentration was much higher than those in mammals. Low [Na⁺]_o evoked [Ca²⁺]_i increases in cDRG neurons in a decreasing [Na⁺]_o-dependent manner and the complete removal of [Na⁺]_o (0Na) produced maximal effects. The population of 0Na-sensitive neurons was mostly overlapped with those of proton- and capsaicin-sensitive ones. Low [Na⁺]_o synergistically potentiated the capsaicin- and proton-induced TRPV1 activation in cDRG neurons. In HEK293 cells expressing cTRPV1 (cTRPV1-HEK), capsaicin elicited [Ca²⁺]_i increases with an EC₅₀ of 11.8 µM, and low [Na⁺]_o also did. Well-defined mammalian TRPV1 antagonists hardly suppressed cTRPV1 activation by low [Na⁺]_o. 0Na evoked outwardly rectified currents in cTRPV1-HEK. Mutagenesis analyses revealed a possible interaction of [Na⁺]_o with the proton-binding sites of cTRPV1. The administration of capsaicin and 0Na to chick eyes elicited pain-related behaviors. These results suggest that low [Na⁺]_o is capable of activating cTRPV1 in vitro, resulting in pain in vivo. Our data demonstrate that characterization of the cTRPV1 function is important to understand activation mechanisms of TRPV1.

瞬时受体电位香草素 1 (TRPV1) 是一种非选择性阳离子通道，主要在伤害性初级感觉神经元中表达。众所周知，TRPV1 对几种刺激的敏感性因物种而异，特别是鸟类直向同源物对辣椒素几乎不敏感。细胞外钠离子 ([Na ⁺ ] _o ) 调节哺乳动物的 TRPV1 活性，但它们对鸡 TRPV1 (cTRPV1) 的调节作用尚不清楚。在这里，我们专注于辣椒素和低 [Na ⁺ ] _o对 cTRPV1 活性的作用。在鸡背根神经节（cDRG）神经元中，辣椒素引起的[Ca ²⁺ ] _i增加，但其有效浓度远高于哺乳动物。低 [Na ⁺] _o诱发的[Ca ²⁺ ] _i在cDRG 神经元中以降低的[Na ⁺ ] _o依赖性方式增加，并且完全去除[Na ⁺ ] _o (0Na) 产生了最大的效果。0Na 敏感神经元的种群主要与质子和辣椒素敏感神经元的种群重叠。低 [Na ⁺ ] _o协同增强 cDRG 神经元中辣椒素和质子诱导的 TRPV1 激活。在表达 cTRPV1 (cTRPV1-HEK) 的 HEK293 细胞中，辣椒素引起 [Ca ²⁺ ] _i增加，EC ₅₀为 11.8 µM，[Na ⁺ ] _o低也做了。定义明确的哺乳动物 TRPV1 拮抗剂很难通过低 [Na ⁺ ] _o抑制 cTRPV1 激活。0Na 在 cTRPV1-HEK 中诱发了向外整流的电流。诱变分析揭示了 [Na ⁺ ] _{o 可能}与 cTRPV1 的质子结合位点相互作用。将辣椒素和 0Na 施用于小鸡眼睛会引起与疼痛相关的行为。这些结果表明低[Na ⁺ ] _o能够在体外激活cTRPV1，导致体内疼痛。我们的数据表明 cTRPV1 功能的表征对于理解 TRPV1 的激活机制很重要。