P2RX2 and P2RX4 receptors mediate cation absorption in transitional cells and supporting cells of the utricular macula
Autor: | Daniel C. Marcus, Jae Young Choi, Jinsei Jung, Jin Young Kim, Junhui Jeong, Sung Huhn Kim, Philine Wangemann, Hansol Hong |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Purinergic P2X Receptor Antagonists Suramin Mice Transgenic Stimulation Membrane Potentials Purinergic P2X Receptor Agonists Purinergic Agonists 03 medical and health sciences chemistry.chemical_compound Adenosine Triphosphate 0302 clinical medicine medicine Animals PPADS Inner ear Saccule and Utricle Receptor Cochlea Purinergic receptor Labyrinth Supporting Cells Sensory Systems Cell biology Drug Partial Agonism Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure chemistry Sulfate Transporters sense organs Receptors Purinergic P2X4 030217 neurology & neurosurgery Receptors Purinergic P2X2 Signal Transduction medicine.drug |
Zdroj: | Hearing Research. 386:107860 |
ISSN: | 0378-5955 |
DOI: | 10.1016/j.heares.2019.107860 |
Popis: | 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. |
Databáze: | OpenAIRE |
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