Authors: V Khmyz O Maximyuk V Teslenko A Verkhratsky O Krishtal
Publish Date: 2007/11/20
Volume: 456, Issue: 2, Pages: 339-347
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 usedependent inhibition by low nanomolar concentrations of ATP through developing the “highaffinity binding site” HABS which traps ATP molecules thus keeping receptors in a desensitized state Pratt et al J Neurosci 257359–7365 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 32 ± 03 nM at 35°C and 079 ± 009 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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