Purinergic Modulation of Cochlear Partition Resistance and Its Effect on the Endocochlear Potential in the Guinea Pig

Abstract

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 kX) 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.

Reduced P2x2 receptor-mediated regulation of endocochlear potential in the ageing mouse cochlea

“…Purinergic signalling appears to be involved in the regulation of hearing sensitivity under stress conditions, acting via the P2X 2 subtype of the receptor in tissues lining the endolymphatic compartment [2,5]. There is increasing evidence that ATP is a neuromodulator at the primary synapse between the inner hair cell and auditory afferent neurones [6] and is a neurotransmitter at the type II synapse with the outer hair cells [7] which regulates the generation of spontaneous neural activity in the developing cochlea [8].…”

“…Exogenous ATP delivered to the scala media in guinea pigs [5] results in a dose-dependent decrease in the endocochlear potential (EP) which is highly correlated with a decrease in resistance of the endolymphatic compartment (cochlear partition resistance, CoPR). This is due to the action of ATP on the ATP-gated ion channels (P2X 2 receptors) present on the apical surface of hair cells and some supporting cells of the organ of Corti and epithelial cells of Reissner's membrane [17].…”

“…This is due to the action of ATP on the ATP-gated ion channels (P2X 2 receptors) present on the apical surface of hair cells and some supporting cells of the organ of Corti and epithelial cells of Reissner's membrane [17]. This is supported by the attenuation of the response with the application of the broadly selective P2X 2 antagonist pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonate (PPADS) [5]. Activation of these receptors by ATP leads to increased potassium flux through these ion channels, causing cellular depolarisation, and the decreased resistance rapidly reduces the EP.…”

“…It has been proposed that ATP released into the endolymph from cells of the organ of Corti or the stria vascularis, following noise or hypoxia, acts via these P2X receptors on cells lining the endolymphatic compartment to limit hearing sensitivity [2,5]. This is accomplished by a combined depolarising action on the sensory cells and suppression of the EP to reduce the driving force for sound transduction by hair cells.…”

“…This is accomplished by a combined depolarising action on the sensory cells and suppression of the EP to reduce the driving force for sound transduction by hair cells. It is postulated that this purinergic pathway is an adaptive, protective mechanism to enable the cochlea to cope with a broad range of sound levels [2,4,5]. Such a mechanism may offer protection, over time, to the sensory cells by reducing their activity under noisy conditions and thus protecting them from damage, for example, from activity-induced free radical exposure.…”