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P2X3 receptor gating near normal body temperature.
Pflugers Arch 2008; 456(2):339-47PA

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 degrees C, whereas the recovery from desensitization is greatly \accelerated with temperature increase (Q10 approximately 10). The sensitivity of HABS to low nanomolar ATP near normal body temperature (35 degrees C) is substantially lower than at 25 degrees C (IC50 is 3.2+/-0.3 nM at 35 degrees C and 0.79+/-0.09 nM at 25 degrees C). HABS itself is subjected to slow desensitization partially loosing its sensitivity to ATP: at 35 degrees 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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18026985

Citation

Khmyz, V, et al. "P2X3 Receptor Gating Near Normal Body Temperature." Pflugers Archiv : European Journal of Physiology, vol. 456, no. 2, 2008, pp. 339-47.
Khmyz V, Maximyuk O, Teslenko V, et al. P2X3 receptor gating near normal body temperature. Pflugers Arch. 2008;456(2):339-47.
Khmyz, V., Maximyuk, O., Teslenko, V., Verkhratsky, A., & Krishtal, O. (2008). P2X3 receptor gating near normal body temperature. Pflugers Archiv : European Journal of Physiology, 456(2), pp. 339-47.
Khmyz V, et al. P2X3 Receptor Gating Near Normal Body Temperature. Pflugers Arch. 2008;456(2):339-47. PubMed PMID: 18026985.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - P2X3 receptor gating near normal body temperature. AU - Khmyz,V, AU - Maximyuk,O, AU - Teslenko,V, AU - Verkhratsky,A, AU - Krishtal,O, Y1 - 2007/11/20/ PY - 2007/09/26/received PY - 2007/10/19/accepted PY - 2007/11/21/pubmed PY - 2008/8/13/medline PY - 2007/11/21/entrez SP - 339 EP - 47 JF - Pflugers Archiv : European journal of physiology JO - Pflugers Arch. VL - 456 IS - 2 N2 - 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 degrees C, whereas the recovery from desensitization is greatly \accelerated with temperature increase (Q10 approximately 10). The sensitivity of HABS to low nanomolar ATP near normal body temperature (35 degrees C) is substantially lower than at 25 degrees C (IC50 is 3.2+/-0.3 nM at 35 degrees C and 0.79+/-0.09 nM at 25 degrees C). HABS itself is subjected to slow desensitization partially loosing its sensitivity to ATP: at 35 degrees 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. SN - 0031-6768 UR - https://www.unboundmedicine.com/medline/citation/18026985/P2X3_receptor_gating_near_normal_body_temperature_ L2 - https://dx.doi.org/10.1007/s00424-007-0376-2 DB - PRIME DP - Unbound Medicine ER -