Characterization of ATPase activity of P2RX2 cation channel

Rahul Mittal, M'hamed Grati, Miloslav Sedlacek, Fenghua Yuan, Qing Chang, Denise Yan, Xi Lin, Bechara Kachar, Amjad Farooq, Prem Chapagain, Yanbin Zhang, Xue Z Liu

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

P2X purinergic receptors are plasma membrane ATP-dependent cation channels that are broadly distributed in the mammalian tissues. P2RX2 is a modulator of auditory sensory hair cell mechanotransduction and plays an important role in hair cell tolerance to noise. In this study, we demonstrate for the first time in vitro and in cochlear neuroepithelium, that P2RX2 possesses the ATPase activity. We observed that the P2RX2 V60L human deafness mutation alters its ability to bind ATP, while the G353R has no effect on ATP binding or hydrolysis. A non-hydrolysable ATP assay using HEK293 cells suggests that ATP hydrolysis plays a significant role in the opening and gating of the P2RX2 ion channel. Moreover, the results of structural modeling of the molecule was in agreement with our experimental observations. These novel findings suggest the intrinsic ATPase activity of P2RX2 and provide molecular insights into the channel opening.

Original languageEnglish (US)
Article number186
JournalFrontiers in Physiology
Volume7
Issue numberMAY
DOIs
StatePublished - 2016

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Adenosine Triphosphatases
Cations
Adenosine Triphosphate
Ion Channel Gating
Hydrolysis
Purinergic P2X Receptors
Auditory Hair Cells
HEK293 Cells
Cochlea
Deafness
Noise
Cell Membrane
Mutation

Keywords

  • ATPase activity
  • Computer modeling
  • Electrophysiology
  • Ligand-gated ion channels
  • P2X2

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Characterization of ATPase activity of P2RX2 cation channel. / Mittal, Rahul; Grati, M'hamed; Sedlacek, Miloslav; Yuan, Fenghua; Chang, Qing; Yan, Denise; Lin, Xi; Kachar, Bechara; Farooq, Amjad; Chapagain, Prem; Zhang, Yanbin; Liu, Xue Z.

In: Frontiers in Physiology, Vol. 7, No. MAY, 186, 2016.

Research output: Contribution to journalArticle

Mittal, R, Grati, M, Sedlacek, M, Yuan, F, Chang, Q, Yan, D, Lin, X, Kachar, B, Farooq, A, Chapagain, P, Zhang, Y & Liu, XZ 2016, 'Characterization of ATPase activity of P2RX2 cation channel', Frontiers in Physiology, vol. 7, no. MAY, 186. https://doi.org/10.3389/fphys.2016.00186
Mittal, Rahul ; Grati, M'hamed ; Sedlacek, Miloslav ; Yuan, Fenghua ; Chang, Qing ; Yan, Denise ; Lin, Xi ; Kachar, Bechara ; Farooq, Amjad ; Chapagain, Prem ; Zhang, Yanbin ; Liu, Xue Z. / Characterization of ATPase activity of P2RX2 cation channel. In: Frontiers in Physiology. 2016 ; Vol. 7, No. MAY.
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AU - Yan, Denise

AU - Lin, Xi

AU - Kachar, Bechara

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