Urine-derived compound evokes membrane responses in mouse vomeronasal receptor neurons

Sensory neurons of the vomeronasal organ (VNO) are thought to detect species-specific chemical signals important for reproductive function. The electrical properties of VNO neurons have begun to be characterized in a variety of species; however, the response of VNO neurons to possible physiological ligands has not yet been reported. One physiological effector, dehydro-exo-brevicomin (DHB), is found in the urine of intact male mice and affects the estrous cycle of female mice. In the present study, dissociated VNO neurons were voltage- or current-clamped and their response to DHB was determined. Approximately 26% of VNO neurons responded to DHB with an outward current at negative holding potentials; the current reversed at approximately +4 mV. Application of DHB in current-clamp mode produced membrane hyperpolarization and/or a reduction in the firing of action potentials. Because membrane conductance was shown to be decreased during application of DHB, the results suggest that the outward current associated with DHB application is a reflection of a reduction in inward current caused by closing an ion channel. This study provides the first evidence that a compound found in male urine directly affects VNO neurons.