Purinergic modulation of cochlear partition resistance and its effect on the endocochlear potential in the Guinea pig

Introduction of adenosine 5'-triphosphate (ATP) into the endolymphatic compartment of the guinea-pig cochlea decreases the endocochlear potential (EP). To determine if this is due to an ATP-induced change in compartment resistance, the cochlear partition resistance (CoPR) was measured using constant current injections into scala media before, during, and after microinjection of ATP into the same compartment. The CoPR (mean = 3.13 +/- 0.13 kOmega) decreased with ATP in a dose-dependent manner (25.1 +/- 3.0% decrease in relation to baseline values) and this was linearly correlated ( R(2) = 0.91) to the magnitude of the ATP-induced decline in EP (41.6 +/- 7.0% decline in relation to the baseline). Pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, a P2X receptor antagonist) injected prior to ATP application blocked this ATP-induced reduction in EP and CoPR. This indicates that ATP-gated ion channels (P2X receptors) provide a latent shunt capable of regulating the majority of the electrical potential across the luminal surface of the sensory hair cells, which is necessary for sound transduction. The results suggest a novel sound transduction regulatory mechanism, which, via extracellular ATP, has the capability of adjusting hearing sensitivity.