Pharmacological evidence that endogenous ATP modulates cochlear mechanics.
In the cochlea, outer hair cells (OHCs) and Deiters' cells most likely contribute to the generation of active cochlear mechanics. The presence of ATP receptors on these cells indicates that endogenous ATP may have a role in cochlear mechanics. To explore this possibility, the effects of ATP antagonists were studied both in vivo on distortion product otoacoustic emissions (DPOAEs) using cochlear perfusion and in vitro on isolated OHCs and Deiters' cells using the whole-cell configuration of the patch-clamp technique. Results show that extracellular application of 5-10 microM ATP to OHCs and Deiters' cells induced an inward current that was reduced by both suramin (100 microM) and cibacron (100 microM). Cibacron reduced the voltage gated currents in Deiters' cells and increased them in OHCs, while suramin had no effect. In addition, cibacron induced a hyperpolarizing shift of the half activation voltage of the whole cell currents in Deiters' cells. Suramin (0.1-1 mM) reversibly suppressed the 'slow decline' in the quadratic DPOAE that occurs during continuous stimulation with moderate level primaries. This effect of suramin may be evidence that endogenous ATP alters active cochlear mechanics.
Skellett
R A
RA
Department of Otorhinolaryngology and Biocommunication, Louisiana State University Medical Center, New Orleans 70112-2234, USA.
Chen
C
C
Fallon
M
M
Nenov
A P
AP
Bobbin
R P
RP
D000161:Acoustic Stimulation; D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D002469:Cell Separation; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects*; D008297:Male; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011500:Protein Synthesis Inhibitors / Q000008:administration & dosage; D058919:Purinergic P2 Receptor Antagonists; D013498:Suramin / Q000008:administration & dosage; D014227:Triazines / Q000008:administration & dosage; D003689:Vestibular Nucleus, Lateral / Q000187:drug effects*
D011500:Protein Synthesis Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D014227:Triazines; C012842:Cibacron Blue F 3GA; D013498:Suramin; D000255:Adenosine Triphosphate