title: Dopamine Modulates the Activity of Sensory Hair Cells.
abstract: The senses of hearing and balance are subject to modulation by efferent signaling, including the release of dopamine (DA). How DA influences the activity of the auditory and vestibular systems and its site of action are not well understood. Here we show that dopaminergic efferent fibers innervate the acousticolateralis epithelium of the zebrafish during development but do not directly form synapses with hair cells. However, a member of the D1-like receptor family, D1b, tightly localizes to ribbon synapses in inner ear and lateral-line hair cells. To assess modulation of hair-cell activity, we reversibly activated or inhibited D1-like receptors (D1Rs) in lateral-line hair cells. In extracellular recordings from hair cells, we observed that D1R agonist SKF-38393 increased microphonic potentials, whereas D1R antagonist SCH-23390 decreased microphonic potentials. Using ratiometric calcium imaging, we found that increased D1R activity resulted in larger calcium transients in hair cells. The increase of intracellular calcium requires Cav1.3a channels, as a Cav1 calcium channel antagonist, isradipine, blocked the increase in calcium transients elicited by the agonist SKF-38393. Collectively, our results suggest that DA is released in a paracrine fashion and acts at ribbon synapses, likely enhancing the activity of presynaptic Cav1.3a channels and thereby increasing neurotransmission.
  
  
  CONCLUSIONS
  The neurotransmitter dopamine acts in a paracrine fashion (diffusion over a short distance) in several tissues and bodily organs, influencing and regulating their activity. The cellular target and mechanism of the action of dopamine in mechanosensory organs, such as the inner ear and lateral-line organ, is not clearly understood. Here we demonstrate that dopamine receptors are present in sensory hair cells at synaptic sites that are required for signaling to the brain. When nearby neurons release dopamine, activation of the dopamine receptors increases the activity of these mechanosensitive cells. The mechanism of dopamine activation requires voltage-gated calcium channels that are also present at hair-cell synapses.
authors.affiliation: Oregon Hearing Research Center and the Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239.
authors.forename: Cecilia
authors.identifier: http://orcid.org/0000-0003-2241-432X
authors.initials: C
authors.lastname: Toro
authors.affiliation: Oregon Hearing Research Center and the Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239.
authors.forename: Josef G
authors.identifier: http://orcid.org/0000-0002-6898-649X
authors.initials: JG
authors.lastname: Trapani
authors.affiliation: Oregon Hearing Research Center and the Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239.
authors.forename: Itallia
authors.initials: I
authors.lastname: Pacentine
authors.affiliation: Oregon Hearing Research Center and the Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239.
authors.forename: Reo
authors.initials: R
authors.lastname: Maeda
authors.affiliation: Oregon Hearing Research Center and the Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Sheets
authors.affiliation: Oregon Hearing Research Center and the Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239.
authors.forename: Weike
authors.initials: W
authors.lastname: Mo
authors.affiliation: Oregon Hearing Research Center and the Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239 nicolson@ohsu.edu.
authors.forename: Teresa
authors.identifier: http://orcid.org/0000-0002-0873-1583
authors.initials: T
authors.lastname: Nicolson
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects; D003055:Cochlear Microphonic Potentials / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000502:physiology*; D006198:Hair Cells, Auditory / Q000502:physiology*; D053403:Lateral Line System / Q000294:innervation / Q000502:physiology; D010739:Phospholipase D / Q000235:genetics / Q000502:physiology; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D015027:Zebrafish / Q000502:physiology*; D029961:Zebrafish Proteins
chemical_list: D001552:Benzazepines; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; C534628:SCH 23390; D029961:Zebrafish Proteins; C488619:cacna1da protein, zebrafish; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D010739:Phospholipase D; C106801:phospholipase D1; D004298:Dopamine
keywords: D1 receptor; dopamine; efferents; hair cell; lateral-line organ; zebrafish