Reduction of extracellular sodium evokes nociceptive behaviors in the chicken via activation of TRPV1.

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 [Ca ²⁺ ] _i increases, but its effective concentration was much higher than those in mammals. Low [Na ⁺ ] _o evoked [Ca ²⁺ ] _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 [Ca ²⁺ ] _i increases with an EC ₅₀ 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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