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- W4319928916 abstract "P2X receptors are ligand-gated ion channels activated by extracellular ATP. They are permeable to small monovalent cations, some having significant divalent or anion permeability. The P2X2 and P2X3 subunits are predominantly expressed in primary sensory neurons and have been proposed to play a role in thermal sensation, taste and pain. They form functional hetero- or homotrimers which are activated by αβ-methylene ATP (αβmeATP). The stoichiometry of P2X2/3 heteromers appears to be dependent on the relative abundance of the two subunits. A mixture of P2X2 and P2X3 homomers as well as P2X2/3 heteromers are likely to coexist but can be distinguished through their biophysical and pharmacological properties. The receptors open in response to an increase in extracellular ATP occurring under pathological conditions. The resulting depolarization leads to propagation of the pain signal. Due to its role in nociception and pain signaling, these receptors are important targets for pain management. Here we present data collected on automated patch clamp (APC) systems with ranging throughput from 1 up to 384 cells simultaneously. We show activation and inhibition of P2X2/3 and P2X3 receptors expressed in CHO cells with rapid and brief application of ligand. ATP was applied using the perfusion system of the Port-a-Patch or the pipette(s) of the Patchliner or SyncroPatch 384. The EC50 values for αβmeATP or ATP activation of P2X2/3 receptors were similar across the three devices. The kinetics of currents mediated by homomeric P2X3 receptors were distinctly faster than those of heteromeric receptors. P2X3-mediated currents activated by αβmeATP could be repetitively activated at least 6 times in the same cell with similar peak amplitudes. The P2X3-selective compound A-317491 blocked P2X3-mediated currents activated by αβmeATP with an IC50 of approximately 90 nM and was similar on all three devices." @default.
- W4319928916 created "2023-02-11" @default.
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- W4319928916 date "2023-02-01" @default.
- W4319928916 modified "2023-10-18" @default.
- W4319928916 title "Pharmacology of P2X3 and P2X2/3 receptors: An automated patch clamp study" @default.
- W4319928916 doi "https://doi.org/10.1016/j.bpj.2022.11.1450" @default.
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