Inhibition of Ionic Currents by Fluoxetine in Vestibular Calyces in Different Epithelial Loci
Abstract
:1. Introduction
2. Results
2.1. K+ Conductances in PZ and CZ Calyces
2.2. Effects of Fluoxetine on the Outward K+ Current in PZ and CZ Calyces
2.3. Effects of Fluoxetine and 4-Aminopyridine (4-AP) in PZ Calyces
2.4. Effects of Fluoxetine on Transient Na+ Currents in CZ and PZ Calyces
2.5. Dose-Dependent Effects of Fluoxetine on K+ and Na+ Currents
2.6. Effect of Fluoxetine on Outward K+ Currents in Vestibular Hair Cells
3. Discussion
3.1. Fluoxetine Blocks Outward K+ Currents in Vestibular Afferent Terminals
3.2. Fluoxetine Blocks Inward Na+ Currents in Vestibular Afferent Terminals
3.3. Fluoxetine Does Not Modulate K+ Currents in Vestibular Hair Cells
3.4. Therapeutic Relevance
4. Materials and Methods
4.1. Crista Extraction
4.2. Slice Preparation
4.3. Isolated Cells Preparation
4.4. Electrophysiological Recordings
4.5. Pharmacological Agents
4.6. Data Analysis
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Simon, N.M.; Parker, S.W.; Wernick-Robinson, M.; Oppenheimer, J.E.; Hoge, E.A.; Worthington, J.J.; Korbly, N.B.; Pollack, M.H. Fluoxetine for vestibular dysfunction and anxiety: A prospective pilot study. Psychosomatics 2005, 46, 334–339. [Google Scholar] [CrossRef] [PubMed]
- Tang, B.; Jiang, W.; Zhang, C.; Tan, H.; Luo, M.; He, Y.; Yu, X. Effect of public square dancing combined with serotonin reuptake inhibitors on persistent postural-perceptual dizziness (PPPD) in middle-aged and older women. J. Vestib. Res. 2024, 34, 63–72. [Google Scholar] [CrossRef] [PubMed]
- Fava, G.A.; Benasi, G.; Lucente, M.; Offidani, E.; Cosci, F.; Guidi, J. Withdrawal Symptoms after Serotonin-Noradrenaline Reuptake Inhibitor Discontinuation: Systematic Review. Psychother. Psychosom. 2018, 87, 195–203. [Google Scholar] [CrossRef] [PubMed]
- Horowitz, M.A.; Taylor, D. Tapering of SSRI treatment to mitigate withdrawal symptoms. Lancet Psychiatry 2019, 6, 538–546. [Google Scholar] [CrossRef] [PubMed]
- Lysakowski, A.; Goldberg, J.M. Ultrastructural analysis of the cristae ampullares in the squirrel monkey (Saimiri sciureus). J. Comp. Neurol. 2008, 511, 47–64. [Google Scholar] [CrossRef]
- Goldberg, J.M. Afferent diversity and the organization of central vestibular pathways. Exp. Brain Res. 2000, 130, 277–297. [Google Scholar] [CrossRef] [PubMed]
- Horwitz, G.C.; Risner-Janiczek, J.R.; Holt, J.R. Mechanotransduction and hyperpolarization-activated currents contribute to spontaneous activity in mouse vestibular ganglion neurons. J. Gen. Physiol. 2014, 143, 481–497. [Google Scholar] [CrossRef] [PubMed]
- Meredith, F.L.; Benke, T.A.; Rennie, K.J. Hyperpolarization-activated current (I h) in vestibular calyx terminals: Characterization and role in shaping postsynaptic events. J. Assoc. Res. Otolaryngol. 2012, 13, 745–758. [Google Scholar] [CrossRef] [PubMed]
- Meredith, F.L.; Kirk, M.E.; Rennie, K.J. Kv1 channels and neural processing in vestibular calyx afferents. Front. Syst. Neurosci. 2015, 9, 85. [Google Scholar] [CrossRef]
- Meredith, F.L.; Rennie, K.J. Persistent and resurgent Na(+) currents in vestibular calyx afferents. J. Neurophysiol. 2020, 124, 510–524. [Google Scholar] [CrossRef]
- Meredith, F.L.; Vu, T.A.; Gehrke, B.; Benke, T.A.; Dondzillo, A.; Rennie, K.J. Expression of hyperpolarization-activated current (I h) in zonally defined vestibular calyx terminals of the crista. J. Neurophysiol. 2023, 129, 1468–1481. [Google Scholar] [CrossRef]
- Ramakrishna, Y.; Manca, M.; Glowatzki, E.; Sadeghi, S.G. Cholinergic modulation of membrane properties of calyx terminals in the vestibular periphery. Neuroscience 2021, 452, 98–110. [Google Scholar] [CrossRef] [PubMed]
- Sadeghi, S.G.; Pyott, S.J.; Yu, Z.; Glowatzki, E. Glutamatergic Signaling at the Vestibular Hair Cell Calyx Synapse. J. Neurosci. 2014, 34, 14536–14550. [Google Scholar] [CrossRef] [PubMed]
- Songer, J.E.; Eatock, R.A. Tuning and timing in mammalian type I hair cells and calyceal synapses. J. Neurosci. 2013, 33, 3706–3724. [Google Scholar] [CrossRef] [PubMed]
- Choi, B.H.; Choi, J.-S.; Yoon, S.H.; Rhie, D.-J.; Jo, Y.-H.; Kim, M.-S.; Hahn, S.J. Effects of norfluoxetine, the major metabolite of fluoxetine, on the cloned neuronal potassium channel Kv3. 1. Neuropharmacology 2001, 41, 443–453. [Google Scholar] [CrossRef] [PubMed]
- Sung, M.J.; Ahn, H.S.; Hahn, S.J.; Choi, B.H. Open channel block of Kv3.1 currents by fluoxetine. J. Pharmacol. Sci. 2008, 106, 38–45. [Google Scholar] [CrossRef] [PubMed]
- Rae, J.L.; Rich, A.; Zamudio, A.C.; Candia, O.A. Effect of Prozac on whole cell ionic currents in lens and corneal epithelia. Am. J. Physiol. Cell Physiol. 1995, 269, C250–C256. [Google Scholar] [CrossRef] [PubMed]
- Tytgat, J.; Maertens, C.; Daenens, P. Effect of fluoxetine on a neuronal, voltage-dependent potassium channel (Kv1.1). Br. J. Pharmacol. 1997, 122, 1417–1424. [Google Scholar] [CrossRef] [PubMed]
- Meredith, F.L.; Rennie, K.J. Zonal variations in K+ currents in vestibular crista calyx terminals. J. Neurophysiol. 2015, 113, 264–276. [Google Scholar] [CrossRef]
- Dhawan, R.; Mann, S.E.; Meredith, F.L.; Rennie, K.J. K+ currents in isolated vestibular afferent calyx terminals. J. Assoc. Res. Otolaryngol. 2010, 11, 463–476. [Google Scholar] [CrossRef]
- Hurley, K.M.; Gaboyard, S.; Zhong, M.; Price, S.D.; Wooltorton, J.R.; Lysakowski, A.; Eatock, R.A. M-like K+ currents in type I hair cells and calyx afferent endings of the developing rat utricle. J. Neurosci. 2006, 26, 10253–10269. [Google Scholar] [CrossRef] [PubMed]
- Chabbert, C.; Chambard, J.M.; Sans, A.; Desmadryl, G. Three Types of Depolarization-Activated Potassium Currents in Acutely Isolated Mouse Vestibular Neurons. J. Neurophysiol. 2001, 85, 1017–1026. [Google Scholar] [CrossRef] [PubMed]
- Limón, A.; Pérez, C.; Vega, R.; Soto, E. Ca2+-Activated K+-Current Density Is Correlated With Soma Size in Rat Vestibular-Afferent Neurons in Culture. J. Neurophysiol. 2005, 94, 3751–3761. [Google Scholar] [CrossRef] [PubMed]
- Risner, J.R.; Holt, J.R. Heterogeneous Potassium Conductances Contribute to the Diverse Firing Properties of Postnatal Mouse Vestibular Ganglion Neurons. J. Neurophysiol. 2006, 96, 2364–2376. [Google Scholar] [CrossRef] [PubMed]
- Rennie, K.J.; Streeter, M.A. Voltage-dependent currents in isolated vestibular afferent calyx terminals. J. Neurophysiol. 2006, 95, 26–32. [Google Scholar] [CrossRef] [PubMed]
- Meredith, F.; Rennie, K. Regional and Developmental Differences in Na+ Currents in Vestibular Primary Afferent Neurons. Front. Cell. Neurosci. 2018, 12, 423. [Google Scholar] [CrossRef] [PubMed]
- Poulin, H.; Theriault, O.; Beaulieu, M.J.; Chahine, M. Fluoxetine blocks Nav1. 5 channels via a mechanism similar to that of class 1 antiarrhythmics. Biophys. J. 2014, 106, 325a–326a. [Google Scholar] [CrossRef]
- Lysakowski, A.; Gaboyard-Niay, S.; Calin-Jageman, I.; Chatlani, S.; Price, S.D.; Eatock, R.A. Molecular microdomains in a sensory terminal, the vestibular calyx ending. J. Neurosci. 2011, 31, 10101–10114. [Google Scholar] [CrossRef] [PubMed]
- Wooltorton, J.R.; Gaboyard, S.; Hurley, K.M.; Price, S.D.; Garcia, J.L.; Zhong, M.; Lysakowski, A.; Eatock, R.A. Developmental changes in two voltage-dependent sodium currents in utricular hair cells. J. Neurophysiol. 2007, 97, 1684–1704. [Google Scholar] [CrossRef]
- Bian, J.-T.; Yeh, J.Z.; Aistrup, G.L.; Narahashi, T.; Moore, E.J. Inhibition of K+ currents of outer hair cells in guinea pig cochlea by fluoxetine. Eur. J. Pharmacol. 2002, 453, 159–166. [Google Scholar] [CrossRef]
- Eatock, R.A.; Songer, J.E. Vestibular hair cells and afferents: Two channels for head motion signals. Annu. Rev. Neurosci. 2011, 34, 501–534. [Google Scholar] [CrossRef] [PubMed]
- Meredith, F.L.; Rennie, K.J. Channeling your inner ear potassium: K+ channels in vestibular hair cells. Hear. Res. 2016, 338, 40–51. [Google Scholar] [CrossRef]
- Correia, M.J.; Lang, D.G. An electrophysiological comparison of solitary type I and type II vestibular hair cells. Neurosci. Lett. 1990, 116, 106–111. [Google Scholar] [CrossRef]
- Rennie, K.J.; Correia, M.J. Potassium currents in mammalian and avian isolated type I semicircular canal hair cells. J. Neurophysiol. 1994, 71, 317–329. [Google Scholar] [CrossRef] [PubMed]
- Rusch, A.; Eatock, R.A. A delayed rectifier conductance in type I hair cells of the mouse utricle. J. Neurophysiol. 1996, 76, 995–1004. [Google Scholar] [CrossRef]
- Martin, H.R.; Lysakowski, A.; Eatock, R.A. The potassium channel subunit KV1.8 (Kcna10) is essential for the distinctive outwardly rectifying conductances of type I and II vestibular hair cells. eLife 2024. [Google Scholar] [CrossRef]
- Meredith, F.L.; Li, G.Q.; Rennie, K.J. Postnatal expression of an apamin-sensitive k(ca) current in vestibular calyx terminals. J. Membr. Biol. 2011, 244, 81–91. [Google Scholar] [CrossRef]
- Spitzmaul, G.; Tolosa, L.; Winkelman, B.H.; Heidenreich, M.; Frens, M.A.; Chabbert, C.; de Zeeuw, C.I.; Jentsch, T.J. Vestibular role of KCNQ4 and KCNQ5 K+ channels revealed by mouse models. J. Biol. Chem. 2013, 288, 9334–9344. [Google Scholar] [CrossRef]
- Kalluri, R.; Xue, J.; Eatock, R.A. Ion channels set spike timing regularity of mammalian vestibular afferent neurons. J. Neurophysiol. 2010, 104, 2034–2051. [Google Scholar] [CrossRef] [PubMed]
- Rocha-Sanchez, S.M.; Morris, K.A.; Kachar, B.; Nichols, D.; Fritzsch, B.; Beisel, K.W. Developmental expression of Kcnq4 in vestibular neurons and neurosensory epithelia. Brain Res. 2007, 1139, 117–125. [Google Scholar] [CrossRef]
- Hight, A.E.; Kalluri, R. A biophysical model examining the role of low-voltage-activated potassium currents in shaping the responses of vestibular ganglion neurons. J. Neurophysiol. 2016, 116, 503–521. [Google Scholar] [CrossRef]
- Brown, D.A.; Passmore, G.M. Neural KCNQ (kv7) channels. Br. J. Pharmacol. 2009, 156, 1185–1195. [Google Scholar] [CrossRef] [PubMed]
- Holt, J.C.; Chatlani, S.; Lysakowski, A.; Goldberg, J.M. Quantal and nonquantal transmission in calyx-bearing fibers of the turtle posterior crista. J. Neurophysiol. 2007, 98, 1083–1101. [Google Scholar] [CrossRef]
- Holt, J.C.; Jordan, P.M.; Lysakowski, A.; Shah, A.; Barsz, K.; Contini, D. Muscarinic acetylcholine receptors and M-currents underlie efferent-mediated slow excitation in calyx-bearing vestibular afferents. J. Neurosci. 2017, 37, 1873–1887. [Google Scholar] [CrossRef] [PubMed]
- Lee, C.; Holt, J.C.; Jones, T.A. Effect of M-current modulation on mammalian vestibular responses to transient head motion. J. Neurophysiol. 2017, 118, 2991–3006. [Google Scholar] [CrossRef] [PubMed]
- Yeung, S.Y.; Millar, J.A.; Mathie, A. Inhibition of neuronal KV potassium currents by the antidepressant drug, fluoxetine. Br. J. Pharmacol. 1999, 128, 1609. [Google Scholar] [CrossRef] [PubMed]
- Choi, J.S.; Hahn, S.J.; Rhie, D.J.; Yoon, S.H.; Jo, Y.H.; Kim, M.S. Mechanism of fluoxetine block of cloned voltage-activated potassium channel Kv1.3. J. Pharmacol. Exp. Ther. 1999, 291, 1–6. [Google Scholar] [PubMed]
- Wang, W.; Yin, H.; Feng, N.; Wang, L.; Wang, X. Inhibitory effects of antidepressant fluoxetine on cloned Kv2. 1 potassium channel expressed in HEK293 cells. Eur. J. Pharmacol. 2020, 878, 173097. [Google Scholar] [CrossRef] [PubMed]
- Hong, H.; Rollman, L.; Feinstein, B.; Sanchez, J.T. Developmental Profile of Ion Channel Specializations in the Avian Nucleus Magnocellularis. Front. Cell Neurosci. 2016, 10, 80. [Google Scholar] [CrossRef]
- Kim, W.B.; Kang, K.-W.; Sharma, K.; Yi, E. Distribution of Kv3 subunits in cochlear afferent and efferent nerve fibers implies distinct role in auditory processing. Exp. Neurobiol. 2020, 29, 344. [Google Scholar] [CrossRef]
- Shrestha, B.R.; Chia, C.; Wu, L.; Kujawa, S.G.; Liberman, M.C.; Goodrich, L.V. Sensory neuron diversity in the inner ear is shaped by activity. Cell 2018, 174, 1229–1246.e1217. [Google Scholar] [CrossRef]
- Iwasaki, S.; Chihara, Y.; Komuta, Y.; Ito, K.; Sahara, Y. Low-voltage-activated potassium channels underlie the regulation of intrinsic firing properties of rat vestibular ganglion cells. J. Neurophysiol. 2008, 100, 2192–2204. [Google Scholar] [CrossRef] [PubMed]
- Liu, X.-P.; Wooltorton, J.R.; Gaboyard-Niay, S.; Yang, F.-C.; Lysakowski, A.; Eatock, R.A. Sodium channel diversity in the vestibular ganglion: NaV1. 5, NaV1. 8, and tetrodotoxin-sensitive currents. J. Neurophysiol. 2016, 115, 2536–2555. [Google Scholar] [CrossRef] [PubMed]
- Quinn, R.K.; Drury, H.R.; Cresswell, E.T.; Tadros, M.A.; Nayagam, B.A.; Callister, R.J.; Brichta, A.M.; Lim, R. Expression and physiology of voltage-gated sodium channels in developing human inner ear. Front. Neurosci. 2021, 15, 733291. [Google Scholar] [CrossRef] [PubMed]
- Thériault, O.; Poulin, H.; Beaulieu, J.-M.; Chahine, M. Differential modulation of Nav1. 7 and Nav1. 8 channels by antidepressant drugs. Eur. J. Pharmacol. 2015, 764, 395–403. [Google Scholar] [CrossRef] [PubMed]
- Tate, K.; Kirk, B.; Tseng, A.; Ulffers, A.; Litwa, K. Effects of the selective serotonin reuptake inhibitor fluoxetine on developing neural circuits in a model of the human fetal cortex. Int. J. Mol. Sci. 2021, 22, 10457. [Google Scholar] [CrossRef] [PubMed]
- Contini, D.; Price, S.D.; Art, J.J. Accumulation of K+ in the synaptic cleft modulates activity by influencing both vestibular hair cell and calyx afferent in the turtle. J. Physiol. 2017, 595, 777–803. [Google Scholar] [CrossRef] [PubMed]
- Contini, D.; Holstein, G.R.; Art, J.J. Synaptic cleft microenvironment influences potassium permeation and synaptic transmission in hair cells surrounded by calyx afferents in the turtle. J. Physiol. 2020, 598, 853–889. [Google Scholar] [CrossRef]
- Dulon, D.; Safieddine, S.; Jones, S.M.; Petit, C. Otoferlin is critical for a highly sensitive and linear calcium-dependent exocytosis at vestibular hair cell ribbon synapses. J. Neurosci. 2009, 29, 10474–10487. [Google Scholar] [CrossRef] [PubMed]
- Highstein, S.M.; Holstein, G.R.; Mann, M.A.; Rabbitt, R.D. Evidence that protons act as neurotransmitters at vestibular hair cell–calyx afferent synapses. Proc. Natl. Acad. Sci. USA 2014, 111, 5421–5426. [Google Scholar] [CrossRef]
- Highstein, S.M.; Mann, M.A.; Holstein, G.R.; Rabbitt, R.D. The quantal component of synaptic transmission from sensory hair cells to the vestibular calyx. J. Neurophysiol. 2015, 113, 3827–3835. [Google Scholar] [CrossRef]
- Yamashita, M.; Ohmori, H. Synaptic responses to mechanical stimulation in calyceal and bouton type vestibular afferents studied in an isolated preparation of semicircular canal ampullae of chicken. Exp. Brain Res. 1990, 80, 475–488. [Google Scholar] [CrossRef]
- Govindaraju, A.C.; Quraishi, I.H.; Lysakowski, A.; Eatock, R.A.; Raphael, R.M. Nonquantal transmission at the vestibular hair cell–calyx synapse: KLV currents modulate fast electrical and slow K+ potentials. Proc. Natl. Acad. Sci. USA 2023, 120, e2207466120. [Google Scholar] [CrossRef]
- Rennie, K.J.; Weng, T.; Correia, M.J. Effects of KCNQ channel blockers on K(+) currents in vestibular hair cells. Am. J. Physiol. Cell Physiol. 2001, 280, C473–C480. [Google Scholar] [CrossRef]
- Ramos, R.T. Antidepressants and dizziness. J. Psychopharmacol. 2006, 20, 708–713. [Google Scholar] [CrossRef]
- Staab, J.P.; Ruckenstein, M.J.; Solomon, D.; Shepard, N.T. Serotonin Reuptake Inhibitors for Dizziness with Psychiatric Symptoms. Arch. Otolaryngol. Head Neck Surg. 2002, 128, 554–560. [Google Scholar] [CrossRef] [PubMed]
- Schatzberg, A.F.; Haddad, P.; Kaplan, E.M.; Lejoyeux, M.; Rosenbaum, J.F.; Young, A.H.; Zajecka, J. Serotonin reuptake inhibitor discontinuation syndrome: A hypothetical definition. Discontinuation Consensus panel. J. Clin. Psychiatry 1997, 58 (Suppl. 7), 5–10. [Google Scholar]
- Smith, P.F.; Darlington, C.L. A possible explanation for dizziness following SSRI discontinuation. Acta Otolaryngol. 2010, 130, 981–983. [Google Scholar] [CrossRef] [PubMed]
- Altamura, A.C.; Moro, A.R.; Percudani, M. Clinical pharmacokinetics of fluoxetine. Clin. Pharmacokinet. 1994, 26, 201–214. [Google Scholar] [CrossRef]
- Bolo, N.R.; Hodé, Y.; Nédélec, J.-F.; Lainé, E.; Wagner, G.; Macher, J.-P. Brain pharmacokinetics and tissue distribution in vivo of fluvoxamine and fluoxetine by fluorine magnetic resonance spectroscopy. Neuropsychopharmacology 2000, 23, 428–438. [Google Scholar] [CrossRef]
- Henry, M.E.; Schmidt, M.E.; Hennen, J.; Villafuerte, R.A.; Butman, M.L.; Tran, P.; Kerner, L.T.; Cohen, B.; Renshaw, P.F. A comparison of brain and serum pharmacokinetics of R-fluoxetine and racemic fluoxetine: A 19-F MRS study. Neuropsychopharmacology 2005, 30, 1576–1583. [Google Scholar] [CrossRef]
- Desai, S.S.; Ali, H.; Lysakowski, A. Comparative morphology of rodent vestibular periphery. II. Cristae ampullares . J. Neurophysiol. 2005, 93, 267–280. [Google Scholar] [CrossRef] [PubMed]
- Lindeman, H. Regional differences in sensitivity of the vestibular sensory epithelia to ototoxic antibiotics. Acta Oto-Laryngol. 1969, 67, 177–189. [Google Scholar] [CrossRef] [PubMed]
- Li, G.Q.; Meredith, F.L.; Rennie, K.J. Development of K+ and Na+ conductances in rodent postnatal semicircular canal type I hair cells. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2010, 298, R351–R358. [Google Scholar] [CrossRef] [PubMed]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Mohamed, N.M.M.; Meredith, F.L.; Rennie, K.J. Inhibition of Ionic Currents by Fluoxetine in Vestibular Calyces in Different Epithelial Loci. Int. J. Mol. Sci. 2024, 25, 8801. https://doi.org/10.3390/ijms25168801
Mohamed NMM, Meredith FL, Rennie KJ. Inhibition of Ionic Currents by Fluoxetine in Vestibular Calyces in Different Epithelial Loci. International Journal of Molecular Sciences. 2024; 25(16):8801. https://doi.org/10.3390/ijms25168801
Chicago/Turabian StyleMohamed, Nesrien M. M., Frances L. Meredith, and Katherine J. Rennie. 2024. "Inhibition of Ionic Currents by Fluoxetine in Vestibular Calyces in Different Epithelial Loci" International Journal of Molecular Sciences 25, no. 16: 8801. https://doi.org/10.3390/ijms25168801