ADDITIONAL PHARMACOLOGICAL EVIDENCE THAT ENDOGENOUS ATP MODULATES COCHLEAR MECHANICS

In the cochlea, outer hair cells (OHCs) generate the active cochlear m echanics whereas the supporting cells, such as Deiters' cells and Hens en's cells, may play a role in both the active and passive cochlear me chanics. 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, t he 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; summat ing potential, SP; compound action potential, CAP) and distortion prod uct otoacoustic emissions (DPOAEs) using cochlear perilymphatic perfus ion. Results show that PPADS (100 mu M) reduced the inward current evo ked by 5-10 mu M ATP in OHCs, Deiters' cells, Hensen's cells and pilla r cells. This effect of PPADS was slow in onset and was slowly reverse d to a varying degree in the different cell types. In vivo application of PPADS in increasing concentrations reduced the sound evoked CAP, S P and increased N-1 latency starting at about 0.33 mM (SP) and 1 mM (C AP and N-1 latency). PPADS (0.33-1 mM) reversibly suppressed the initi al value of the quadratic DPOAE and reversed the 'slow decline' in the quadratic DPOAE that occurs during continuous stimulation with modera te level primaries. These results, together with the similar effects o f the ATP antagonist suramin reported previously (Skellett et al., 199 7), may be evidence that endogenous ATP acting on cells in the organ o f Corti alters cochlear mechanics. (C) 1998 Elseuier Science B.V.