Extracellular pH regulates excitability of vomeronasal sensory neurons.
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.
Department of Chemosensation, Institute for Biology II, RWTH Aachen University, D-52074 Aachen, Germany.
Annika
A
Cichy
Department of Chemosensation, Institute for Biology II, RWTH Aachen University, D-52074 Aachen, Germany.
Tobias
T
Ackels
Department of Chemosensation, Institute for Biology II, RWTH Aachen University, D-52074 Aachen, Germany.
Chryssanthi
C
Tsitoura
School of Medicine, Department of Medical Neurobiology, The Hebrew University of Jerusalem, Jerusalem, 91120 Israel, and.
Anat
A
Kahan
Department of Chemosensation, Institute for Biology II, RWTH Aachen University, D-52074 Aachen, Germany.
Nina
N
Gronloh
Cellular Biophysics, Institute of Complex Systems, Forschungszentrum Jülich, D-52425 Jülich, Germany.
Melanie
M
Söchtig
Department of Chemosensation, Institute for Biology II, RWTH Aachen University, D-52074 Aachen, Germany.
Corinna H
CH
Engelhardt
School of Medicine, Department of Medical Neurobiology, The Hebrew University of Jerusalem, Jerusalem, 91120 Israel, and.
Yoram
Y
Ben-Shaul
Cellular Biophysics, Institute of Complex Systems, Forschungszentrum Jülich, D-52425 Jülich, Germany.
Frank
F
Müller
Department of Chemosensation, Institute for Biology II, RWTH Aachen University, D-52074 Aachen, Germany.
Jennifer
J
Spehr
Department of Chemosensation, Institute for Biology II, RWTH Aachen University, D-52074 Aachen, Germany, m.spehr@sensorik.rwth-aachen.de.
Marc
http://orcid.org/0000-0001-6616-4196
M
Spehr
D000818:Animals; D004971:Estrus / Q000502:physiology; D005260:Female; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009830:Olfactory Bulb / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D011984:Sensory Receptor Cells / Q000502:physiology*; D050052:TRPC Cation Channels / Q000235:genetics; D019147:Vomeronasal Organ / Q000166:cytology* / Q000502:physiology*
D050052:TRPC Cation Channels; C491858:Trpc2 protein, mouse
HCN; ion channel; signaling; vomeronasal organ