Abstract
Gap junction-mediated K+ recycling in the cochlear supporting cell has been proposed to play a critical role in hearing. However, how potassium ions enter into the supporting cells to recycle K+ remains undetermined. In this paper, we report that ATP can mediate K+ sinking to recycle K+ in the cochlear supporting cells. We found that micromolar or submicromolar levels of ATP could evoke a K+-dependent inward current in the cochlear supporting cells. At negative membrane potentials and the resting membrane potential of −80 mV, the amplitude of the ATP-evoked inward current demonstrated a linear relationship to the extracellular concentration of K+, increasing as the extracellular concentration of K+ increased. The inward current also increased as the concentration of ATP was increased. In the absence of ATP, there was no evoked inward current for extracellular K+ challenge in the cochlear supporting cells. The ATP-evoked inward current could be inhibited by ionotropic purinergic (P2X) receptor antagonists. Application of pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS, 50 µM) or pre-incubation with an irreversible P2X7 antagonist oxidized ATP (oATP, 0.1 mM) completely abolished the ATP-evoked inward current at the negative membrane potential. ATP also evoked an inward current at cell depolarization, which could be inhibited by intracellular Cs+ and eliminated by positive holding potentials. Our data indicate that ATP can activate P2X receptors to recycle K+ in the cochlear supporting cells at the resting membrane potential under normal physiological and pathological conditions. This ATP-mediated K+ recycling may play an important role in the maintenance of cochlear ionic homeostasis.
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This work was supported by NIDCD DC 05989.
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Zhu, Y., Zhao, HB. ATP-mediated potassium recycling in the cochlear supporting cells. Purinergic Signalling 6, 221–229 (2010). https://doi.org/10.1007/s11302-010-9184-9
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DOI: https://doi.org/10.1007/s11302-010-9184-9