Hegg Colleen C, Lucero Mary T
Department of Physiology, University of Utah, Salt Lake City, Utah 84108-1297, USA.
J Neurophysiol. 2004 Apr;91(4):1492-9. doi: 10.1152/jn.00670.2003. Epub 2003 Dec 3.
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.
虽然D2多巴胺受体已定位到嗅觉受体神经元（ORN），并且多巴胺已被证明可调节ORN中的电压门控离子通道，但此前尚未证实多巴胺能对哺乳动物ORN的气味反应或兴奋性进行调节。我们发现，浓度低于50微摩尔的多巴胺可可逆地抑制ORN中气味诱导的Ca2+瞬变。对加载了Ca(2+)指示剂染料fluo-4 AM的新生小鼠嗅觉上皮300微米厚切片进行共聚焦激光成像显示，D2多巴胺受体拮抗剂舒必利（浓度低于500微摩尔）可阻断多巴胺对气味反应的抑制作用。多巴胺诱导的气味反应抑制可被100微摩尔硝苯地平完全逆转，这表明D2受体激活会导致ORN中L型Ca2+通道受到抑制。此外，多巴胺可逆地降低ORN的兴奋性，这可通过响应升高的K(+)时Ca2+瞬变的幅度和频率降低得到证明，升高的K(+)会激活ORN中的电压门控Ca2+通道。与气味反应抑制情况一样，多巴胺对ORN兴奋性的影响可被D2多巴胺受体拮抗剂舒必利（浓度低于500微摩尔）阻断。对ORN中气味诱导的Ca2+瞬变进行多巴胺能调节的观察结果，进一步证明了越来越多的研究表明嗅觉受体神经元可在外周受到调节。鼻黏液中的多巴胺浓度会因有害刺激而增加，因此D2受体介导的电压门控Ca2+通道抑制可能是ORN的一种新型神经保护机制。
