title: ATP-Evoked Intracellular Ca²⁺ Signaling of Different Supporting Cells in the Hearing Mouse Hemicochlea.
abstract: Hearing and its protection is regulated by ATP-evoked Ca(2+) signaling in the supporting cells of the organ of Corti, however, the unique anatomy of the cochlea hampers observing these mechanisms. For the first time, we have performed functional ratiometric Ca(2+) imaging (fura-2) in three different supporting cell types in the hemicochlea preparation of hearing mice to measure purinergic receptor-mediated Ca(2+) signaling in pillar, Deiters' and Hensen's cells. Their resting [Ca(2+)]i was determined and compared in the same type of preparation. ATP evoked reversible, repeatable and dose-dependent Ca(2+) transients in all three cell types, showing desensitization. Inhibiting the Ca(2+) signaling of the ionotropic P2X (omission of extracellular Ca(2+)) and metabotropic P2Y purinergic receptors (depletion of intracellular Ca(2+) stores) revealed the involvement of both receptor types. Detection of P2X2,3,4,6,7 and P2Y1,2,6,12,14 receptor mRNAs by RT-PCR supported this finding and antagonism by PPADS suggested different functional purinergic receptor population in pillar versus Deiters' and Hensen's cells. The sum of the extra- and intracellular Ca(2+)-dependent components of the response was about equal with the control ATP response (linear additivity) in pillar cells, and showed supralinearity in Deiters' and Hensen's cells. Calcium-induced calcium release might explain this synergistic interaction. The more pronounced Ca(2+) leak from the endoplasmic reticulum in Deiters' and Hensen's cells, unmasked by cyclopiazonic acid, may also suggests the higher activity of the internal stores in Ca(2+) signaling in these cells. Differences in Ca(2+) homeostasis and ATP-induced Ca(2+) signaling might reflect the distinct roles these cells play in cochlear function and pathophysiology.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvárad tér 4., Budapest, 1089, Hungary.|Department of Otorhinolaryngology, Head and Neck Surgery, Bajcsy-Zsilinszky Hospital, Budapest, Hungary.
authors.forename: T
authors.initials: T
authors.lastname: Horváth
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Semmelweis University, Budapest, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Polony
authors.affiliation: Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Á
authors.initials: Á
authors.lastname: Fekete
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvárad tér 4., Budapest, 1089, Hungary.|Computational Cognitive Neuroimaging Laboratory, Computational Neuroscience and Cognitive Robotics Centre, University of Birmingham, Birmingham, UK.
authors.forename: M
authors.initials: M
authors.lastname: Aller
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Halmos
authors.affiliation: Pharmacological and Drug Safety Research, Gedeon Richter Plc., Budapest, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Lendvai
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Heinrich
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Sperlágh
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: E S
authors.initials: ES
authors.lastname: Vizi
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvárad tér 4., Budapest, 1089, Hungary. zelles.tibor@med.semmelweis-univ.hu.|Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary. zelles.tibor@med.semmelweis-univ.hu.
authors.forename: T
authors.initials: T
authors.lastname: Zelles
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D003051:Cochlea / Q000166:cytology / Q000502:physiology*; D005072:Evoked Potentials, Auditory; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D058469:Receptors, Purinergic P2X / Q000235:genetics; D058470:Receptors, Purinergic P2Y / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D058469:Receptors, Purinergic P2X; D058470:Receptors, Purinergic P2Y; D000255:Adenosine Triphosphate
keywords: ATP; Ca2+ imaging; Deiters’ cells; Hemicochlea; Hensen’s cells; Pillar cells