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P2X3 receptor gating near normal body temperature

  • Cellular Neurophysiology
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Abstract

P2X3 purinoreceptors expressed in mammalian sensory neurons are involved in nociception, mechanosensory transduction, and temperature sensation. Homomeric P2X3 receptors desensitize rapidly (<500 ms after activation by an agonist) and recover from desensitization very slowly (20–25 min at room temperature). They are susceptible to use-dependent inhibition by low nanomolar concentrations of ATP through developing the “high-affinity binding site” (HABS), which traps ATP molecules, thus keeping receptors in a desensitized state (Pratt et al., J Neurosci 25:7359–7365, 2005). Indeed, here we demonstrated directly that the desensitization of the receptor, after being activated by ATP, proceeds independently of the presence of agonist. We found that the temperature sensitivity of P2X3 receptors is abnormal: development of desensitization does not depend on temperature within the range between 25 and 40°C, whereas the recovery from desensitization is greatly \accelerated with temperature increase (Q 10 ∼10). The sensitivity of HABS to low nanomolar ATP near normal body temperature (35°C) is substantially lower than at 25°C (IC50 is 3.2 ± 0.3 nM at 35°C and 0.79 ± 0.09 nM at 25°C). HABS itself is subjected to slow desensitization partially loosing its sensitivity to ATP: at 35°C the response completely recovers in 10 min in the presence of 3 nM ATP, making the receptor operational in the presence of up to 30 nM ATP. Unusual combination of temperature sensitivity/insensitivity of P2X3 receptors may be related to their pivotal role in the processing of thermal sensitivity as revealed by recent knockout experiments.

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Acknowledgements

This research was supported by Civilian Research and Development Foundation and Howard Hughes Medical Institute grants to OK and International Association for Cooperation with Scientists from the former Soviet Union grant to OK and AV.

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Authors and Affiliations

  1. Bogomoletz Institute of Physiology, Bogomoletz street 4, Kyiv-24, Ukraine

    V. Khmyz, O. Maximyuk & O. Krishtal

  2. Bogolyubov Institute for Theoretical Physics, Metrologichna street 14-b, Kyiv-143, Ukraine

    V. Teslenko

  3. Faculty of Life Sciences, The University of Manchester, Manchester, M13 9PT, UK

    A. Verkhratsky

  4. Institute of Experimental Medicine, ASCR, Videnska 1083, 142 20, Prague 4, Czech Republic

    A. Verkhratsky

Authors
  1. V. Khmyz
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  2. O. Maximyuk
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  3. V. Teslenko
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  4. A. Verkhratsky
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  5. O. Krishtal
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Correspondence to O. Krishtal.

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Khmyz, V., Maximyuk, O., Teslenko, V. et al. P2X3 receptor gating near normal body temperature. Pflugers Arch - Eur J Physiol 456, 339–347 (2008). https://doi.org/10.1007/s00424-007-0376-2

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  • DOI: https://doi.org/10.1007/s00424-007-0376-2

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