title: Additional pharmacological evidence that endogenous ATP modulates cochlear mechanics.
abstract: In the cochlea, outer hair cells (OHCs) generate the active cochlear mechanics whereas the supporting cells, such as Deiters' cells and Hensen's cells, may play a role in both the active and passive cochlear mechanics. The presence of receptors for adenosine triphosphate (ATP) on OHCs, Deiters' cells and Hensen's cells indicates that endogenous ATP may have a role in cochlear mechanics. To explore this possibility, the effects of the ATP antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), were studied in guinea pig both in vitro on isolated OHCs, Deiters' cells, Hensen's cells and pillar cells using the whole-cell configuration of the patch-clamp technique, and in vivo on sound evoked cochlear potentials (cochlear microphonic, CM; summating potential, SP; compound action potential, CAP) and distortion product otoacoustic emissions (DPOAEs) using cochlear perilymphatic perfusion. Results show that PPADS (100 microM) reduced the inward current evoked by 5-10 microM ATP in OHCs, Deiters' cells, Hensen's cells and pillar cells. This effect of PPADS was slow in onset and was slowly reversed to a varying degree in the different cell types. In vivo application of PPADS in increasing concentrations reduced the sound evoked CAP, SP and increased N1 latency starting at about 0.33 mM (SP) and 1 mM (CAP and N1 latency). PPADS (0.33-1 mM) reversibly suppressed the initial value of the quadratic DPOAE and reversed the 'slow decline' in the quadratic DPOAE that occurs during continuous stimulation with moderate level primaries. These results, together with the similar effects of the ATP antagonist suramin reported previously (Skellett et al., 1997), may be evidence that endogenous ATP acting on cells in the organ of Corti alters cochlear mechanics.
authors.affiliation: Kresge Hearing Research Laboratory of the South, Department of Otorhinolaryngology and Biocommunication, Louisiana State University Medical Center, New Orleans 70112-2234, USA.
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.forename: R A
authors.initials: RA
authors.lastname: Skellett
authors.forename: M
authors.initials: M
authors.lastname: Fallon
authors.forename: R P
authors.initials: RP
authors.lastname: Bobbin
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D003051:Cochlea / Q000187:drug effects* / Q000502:physiology; D003055:Cochlear Microphonic Potentials / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000502:physiology; D009925:Organ of Corti / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D003689:Vestibular Nucleus, Lateral / Q000187:drug effects / Q000502:physiology; D000159:Vestibulocochlear Nerve / Q000187:drug effects / Q000502:physiology
chemical_list: D010975:Platelet Aggregation Inhibitors; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate