P2RX2 and P2RX4 receptors mediate cation absorption in transitional cells and supporting cells of the utricular macula

Abstract

Purinergic receptors protect the cochlea during high-intensity stimulation by providing a parallel shunt pathway through non-sensory neighboring epithelial cells for cation absorption. So far, there is no direct functional evidence for the presence and type/subunit of purinergic receptors in the utricle of the vestibular labyrinth. The goal of the present study was to investigate which purinergic receptors are expressed and carry cation-absorption currents in the utricular transitional cells and macula. Purinergic agonists induced cation-absorption currents with a potency order of ATP > bzATP = αβmeATP ≫ ADP = UTP = UDP. ATP and bzATP are full agonists, whereas αβmeATP is a partial agonist. ATP-induced currents were partially inhibited by 100 μM suramin, 10 μM pyridoxal-phosphate-6-azo-(benzene-2,4-disulfonic acid (PPADS), or 5 μM 5-(3-bromophenyl)-1,3-dihydro-2H-benzofuro[3,2-e]-1, 4-diazepin-2-one (5-BDBD), and almost completely blocked by 100 μM Gd3+ or by a combination of 10 μM PPADS and 5 μM 5-BDBD. Expression of the P2RX2 and P2RX4 receptor was detected by immunocytochemistry in transitional cells and macular supporting cells. This is the first study to demonstrate that ATP induces cation currents carried by a combination of P2RX2 and P2RX4 in utricular transitional and macular epithelial cells, and supporting the hypothesis that purinergic receptors protect utricular hair cells during elevated stimulus intensity levels.