Ca2+ -calmodulin feedback mediates sensory adaptation and inhibits pheromone-sensitive ion channels in the vomeronasal organ.
The mammalian vomeronasal organ (VNO) mediates the regulation of social behaviors by complex chemical signals. These cues trigger transient elevations of intracellular Ca(2+) in vomeronasal sensory neurons (VSNs), but the functional role of such Ca(2+) elevations is unknown. We show that stimulus-induced Ca(2+) entry plays an essential role as a negative feedback regulator of VSN sensitivity. Electrophysiological VSN responses undergo effective sensory adaptation that requires the influx of Ca(2+) and is mediated by calmodulin (CaM). Removal of the Ca(2+)-CaM feedback eliminates this form of adaptation. A key target of this feedback module is the pheromone-sensitive TRPC2-dependent cation channel of VSNs, as its activation is strongly inhibited by Ca(2+)-CaM. Our results reveal a previously unrecognized CaM-signaling pathway that endows the VSNs with a mechanism for adjusting gain and sensitivity of chemosensory signaling in the VNO.
Spehr
Jennifer
J
Department of Cellular Physiology and Emmy Noether Research Group, Ruhr University of Bochum, 44780 Bochum, Germany.
Hagendorf
Silke
S
Weiss
Jan
J
Spehr
Marc
M
Leinders-Zufall
Trese
T
Zufall
Frank
F
D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002147:Calmodulin / Q000378:metabolism*; D005246:Feedback / Q000502:physiology; D005260:Female; D007473:Ion Channels / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010675:Pheromones / Q000502:physiology*; D012677:Sensation / Q000502:physiology; D012903:Smell / Q000502:physiology; D050052:TRPC Cation Channels / Q000378:metabolism; D019147:Vomeronasal Organ / Q000378:metabolism*
D002147:Calmodulin; D007473:Ion Channels; D010675:Pheromones; D050052:TRPC Cation Channels; C491858:Trpc2 protein, mouse; D002118:Calcium