ATP-mediated potassium recycling in the cochlear supporting cells.
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 microM) 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.


BACKGROUND
The online version of this article (doi:10.1007/s11302-010-9184-9) contains supplementary material, which is available to authorized users.
Zhu
Yan
Y
Department of Surgery-Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536-0293 USA.
Zhao
Hong-Bo
HB
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