Dopamine reduces odor- and elevated-K(+)-induced calcium responses in mouse olfactory receptor neurons in situ.
Although D2 dopamine receptors have been localized to olfactory receptor neurons (ORNs) and dopamine has been shown to modulate voltage-gated ion channels in ORNs, dopaminergic modulation of either odor responses or excitability in mammalian ORNs has not previously been demonstrated. We found that <50 microM dopamine reversibly suppresses odor-induced Ca2+ transients in ORNs. Confocal laser imaging of 300-microm-thick slices of neonatal mouse olfactory epithelium loaded with the Ca(2+)-indicator dye fluo-4 AM revealed that dopaminergic suppression of odor responses could be blocked by the D2 dopamine receptor antagonist sulpiride (<500 microM). The dopamine-induced suppression of odor responses was completely reversed by 100 microM nifedipine, suggesting that D2 receptor activation leads to an inhibition of L-type Ca2+ channels in ORNs. In addition, dopamine reversibly reduced ORN excitability as evidenced by reduced amplitude and frequency of Ca2+ transients in response to elevated K(+), which activates voltage-gated Ca2+ channels in ORNs. As with the suppression of odor responses, the effects of dopamine on ORN excitability were blocked by the D2 dopamine receptor antagonist sulpiride (<500 microM). The observation of dopaminergic modulation of odor-induced Ca2+ transients in ORNs adds to the growing body of work showing that olfactory receptor neurons can be modulated at the periphery. Dopamine concentrations in nasal mucus increase in response to noxious stimuli, and thus D2 receptor-mediated suppression of voltage-gated Ca2+ channels may be a novel neuroprotective mechanism for ORNs.
Hegg
Colleen C
CC
Department of Physiology, University of Utah, Salt Lake City, Utah 84108-1297, USA.
Lucero
Mary T
MT
D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D066298:In Vitro Techniques; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods; D009543:Nifedipine / Q000494:pharmacology; D009812:Odorants; D009831:Olfactory Mucosa / Q000166:cytology* / Q000187:drug effects; D018034:Olfactory Receptor Neurons / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology*; D013469:Sulpiride / Q000494:pharmacology; D013997:Time Factors; D014966:Xanthenes / Q000378:metabolism
D000814:Aniline Compounds; D002121:Calcium Channel Blockers; D018492:Dopamine Antagonists; C409648:Fluo 4; D014966:Xanthenes; D013469:Sulpiride; D009543:Nifedipine; D011188:Potassium; D002118:Calcium; D004298:Dopamine