title: Sound-Induced Intracellular Ca2+ Dynamics in the Adult Hearing Cochlea.
abstract: Ca2+ signaling has been implicated in the initial pathophysiologic mechanisms underlying the cochlea's response to acoustic overstimulation. Intracellular Ca2+ signaling (ICS) waves, which occur in glia and retinal cells in response to injury to activate cell regulatory pathways, have been proposed as an early event in cochlear injury. Disruption of ICS activity is thought to underlie Connexin 26-associated hearing loss, the most common genetic form of deafness, and downstream sequelae of ICS wave activity, such as MAP kinase pathway activation, have been implicated in noise-induced hearing loss. However, ICS waves have only been observed in neonatal cochlear cultures and are thought to be quiescent after the onset of hearing. In this study, we employ an acute explant model of an adult, hearing cochlea that retains many in vivo physiologic features to investigate Ca2+ changes in response to sound. We find that both slow monotonic changes in intracellular Ca2+ concentration as well as discrete ICS waves occur with acoustic overstimulation. The ICS waves share many intrinsic features with their better-described neonatal counterparts, including ATP and gap-junction dependence, and propagation velocity and distance. This identification of ICS wave activity in the adult, hearing cochlea thus confirms and characterizes an important early detection mechanism for cochlear trauma and provides a target for interventions for noise-induced and Connexin 26-associated hearing loss.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, United States of America.
authors.forename: Dylan K
authors.initials: DK
authors.lastname: Chan
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, United States of America.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Rouse
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D020013:Calcium Signaling; D002478:Cells, Cultured; D003051:Cochlea / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D005260:Female; D017629:Gap Junctions / Q000378:metabolism; D005849:Gerbillinae; D051379:Mice; D008810:Mice, Inbred C57BL; D013016:Sound
chemical_list: D000255:Adenosine Triphosphate