TY - JOUR T1 - Extracellular pH Regulates Excitability of Vomeronasal Sensory Neurons JF - The Journal of Neuroscience JO - J. Neurosci. SP - 4025 LP - 4039 DO - 10.1523/JNEUROSCI.2593-14.2015 VL - 35 IS - 9 AU - Annika Cichy AU - Tobias Ackels AU - Chryssanthi Tsitoura AU - Anat Kahan AU - Nina Gronloh AU - Melanie Söchtig AU - Corinna H. Engelhardt AU - Yoram Ben-Shaul AU - Frank Müller AU - Jennifer Spehr AU - Marc Spehr Y1 - 2015/03/04 UR - http://www.jneurosci.org/content/35/9/4025.abstract N2 - The mouse vomeronasal organ (VNO) plays a critical role in semiochemical detection and social communication. Vomeronasal stimuli are typically secreted in various body fluids. Following direct contact with urine deposits or other secretions, a peristaltic vascular pump mediates fluid entry into the recipient's VNO. Therefore, while vomeronasal sensory neurons (VSNs) sample various stimulatory semiochemicals dissolved in the intraluminal mucus, they might also be affected by the general physicochemical properties of the “solvent.” Here, we report cycle stage-correlated variations in urinary pH among female mice. Estrus-specific pH decline is observed exclusively in urine samples from sexually experienced females. Moreover, patch-clamp recordings in acute VNO slices reveal that mouse VSNs reliably detect extracellular acidosis. Acid-evoked responses share the biophysical and pharmacological hallmarks of the hyperpolarization-activated current Ih. Mechanistically, VSN acid sensitivity depends on a pH-induced shift in the voltage-dependence of Ih activation that causes the opening of HCN channels at rest, thereby increasing VSN excitability. Together, our results identify extracellular acidification as a potent activator of vomeronasal Ih and suggest HCN channel-dependent vomeronasal gain control of social chemosignaling. Our data thus reveal a potential mechanistic basis for stimulus pH detection in rodent chemosensory communication. ER -