Calcium-activated chloride current amplifies the response to urine in mouse vomeronasal sensory neurons

The vomeronasal organ (VNO) is an odor detection system that mediates many pheromone-sensitive behaviors. Vomeronasal sensory neurons (VSNs), located in the VNO, are the initial site of interaction with odors/pheromones. However, how an individual VSN transduces chemical signals into electrical signals is still unresolved. Here, we show that a Ca(2+)-activated Cl(−) current contributes ∼80% of the response to urine in mouse VSNs. Using perforated patch clamp recordings with gramicidin, which leaves intracellular chloride undisrupted, we found that the urine-induced inward current (V(hold) = −80 mV) was decreased in the presence of chloride channel blockers. This was confirmed using whole cell recordings and altering extracellular chloride to shift the reversal potential. Further, the urine-induced currents were eliminated when both extracellular Ca(2+) and Na(+) were removed. Using inside-out patches from dendritic tips, we recorded Ca(2+)-activated Cl(−) channel activity. Several candidates for this Ca(2+)-activated Cl(−) channel were detected in VNO by reverse transcription–polymerase chain reaction. In addition, a chloride cotransporter, Na(+)-K(+)-2Cl(−) isoform 1, was detected and found to mediate much of the chloride accumulation in VSNs. Collectively, our data demonstrate that chloride acts as a major amplifier for signal transduction in mouse VSNs. This amplification would increase the responsiveness to pheromones or odorants.