Functional ligand-gated purinergic receptors (P2X) in rat vestibular ganglion neurons

Abstract

The expression of purinergic receptors (P2X) on rat vestibular ganglion neurons (VGNs) was examined using whole-cell patch-clamp recordings. An application of adenosine 5′-triphosphate (ATP; 100μM) evoked inward currents in VGNs at a holding potential of −60mV. The decay time constant of the ATP-evoked currents was 2–4s, which is in between the values for rapidly desensitizing subgroups (P2X1 and P2X3) and slowly desensitizing subgroups (P2X2, P2X4, etc.), suggesting the heterogeneous expression of P2X receptors. A dose–response experiment showed an EC50 of 11.0μM and a Hill’s coefficient of 0.82. Suramin (100μM) reversibly inhibited the ATP-evoked inward currents. Alpha, beta-methylene ATP (100μM), a P2X-specific agonist, also evoked inward currents but less extensively than ATP. An application of adenosine 5′-dihosphate (ADP; 100μM) evoked similar, but much smaller, currents. The current–voltage relationship of the ATP-evoked conductance showed pronounced inward rectification with a reversal potential more positive than 0mV, suggesting non-selective cation conductance. However, the channel was not permeable to a large cation (N-methyl-d-glucamine) and acidification (pH 6.3) had little effect on the ATP-evoked conductance. RT-PCR confirmed the expression of five subtypes (P2X2–P2X6) in VGNs. The physiological role of P2X receptors includes the modulation of excitability at the synapses between hair cells and dendrites and/or trophic support (or also neuromodulation) from supporting cells surrounding the VGNs.