Additional pharmacological evidence that endogenous ATP modulates cochlear mechanics

• Published in: Hearing research Vol. 118; no. 1; pp. 47 - 61
• Main Authors: Chen, Chu, Skellett, Ruth A, Fallon, Maureen, Bobbin, Richard P
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.04.1998; Elsevier
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Adenosine Triphosphate - antagonists & inhibitors; Adenosine Triphosphate - physiology; Animals; Biological and medical sciences; Cochlea - drug effects; Cochlea - physiology; Cochlear Microphonic Potentials - drug effects; Cochlear Microphonic Potentials - physiology; Deiters' cell; Ear and associated structures. Auditory pathways and centers. Hearing. Vocal organ. Phonation. Sound production. Echolocation; Fundamental and applied biological sciences. Psychology; Guinea Pigs; Hair Cells, Auditory, Outer - drug effects; Hair Cells, Auditory, Outer - physiology; Hensen's cell; Ion channel; Organ of Corti - cytology; Organ of Corti - drug effects; Organ of Corti - physiology; Otoacoustic emission; Otoacoustic Emissions, Spontaneous - drug effects; Otoacoustic Emissions, Spontaneous - physiology; Outer hair cell; Patch-Clamp Techniques; Pillar cell; Platelet Aggregation Inhibitors - pharmacology; Pyridoxal Phosphate - analogs & derivatives; Pyridoxal Phosphate - pharmacology; Pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid; Vertebrates: nervous system and sense organs; Vestibular Nucleus, Lateral - drug effects; Vestibular Nucleus, Lateral - physiology; Vestibulocochlear Nerve - drug effects; Vestibulocochlear Nerve - physiology; Pillar cell; Otoacoustic emission; Pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid; Ion channel; Deiters' cell; Outer hair cell; Hensen's cell; Cochlear potential; Supporting cell; Rodentia; Electrophysiology; Mechanical properties; Ionic channel; Ionic current; Inner ear; Organ of hearing; Vertebrata; Mammalia; Guinea pig; Purinergic receptor; Cochlea; ATP
• ISSN: 0378-5955; 1878-5891
• DOI: 10.1016/S0378-5955(98)00019-7

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 μM) reduced the inward current evoked by 5–10 μM 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 N 1 latency starting at about 0.33 mM (SP) and 1 mM (CAP and N 1 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.