Epithelial P2X purinergic receptor channel expression and function
Amanda L. Taylor, Lisa M. Schwiebert, Jeffrey J. Smith, Chris King, Julie R. Jones, Eric J. Sorscher, Erik M. Schwiebert
Amanda L. Taylor, Lisa M. Schwiebert, Jeffrey J. Smith, Chris King, Julie R. Jones, Eric J. Sorscher, Erik M. Schwiebert
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Epithelial P2X purinergic receptor channel expression and function

Abstract

P2X purinergic receptor (P2XR) channels bind ATP and mediate Ca2+ influx — 2 signals that stimulate secretory Cl– transport across epithelia. We tested the hypotheses that P2XR channels are expressed by epithelia and that P2XRs transduce extracellular ATP signals into stimulation of Cl– transport across epithelia. Electrophysiological data and mRNA analysis of human and mouse pulmonary epithelia and other epithelial cells indicate that multiple P2XRs are broadly expressed in these tissues and that they are active on both apical and basolateral surfaces. Because P2X-selective agonists bind multiple P2XR subtypes, and because P2X agonists stimulate Cl– transport across nasal mucosa of cystic fibrosis (CF) patients as well as across non-CF nasal mucosa, P2XRs may provide novel targets for extracellular nucleotide therapy of CF.

Authors

Amanda L. Taylor, Lisa M. Schwiebert, Jeffrey J. Smith, Chris King, Julie R. Jones, Eric J. Sorscher, Erik M. Schwiebert

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Extracellular ATP (Ext ATP) stimulates nonselective cation currents in w...
Extracellular ATP (Ext ATP) stimulates nonselective cation currents in whole-cell recordings of non-CF and CF airway epithelial cells. (a) I-V plots of basal and ATP-stimulated nonselective cation currents in ΣCFTE-29o– cells. n = 6, paired recordings. Values are mean ± SEM (*P < 0.05). (b) Typical time course of sustained P2XR current stimulation with 2 doses of ATP ligand, and reversal with suramin, a P2XR antagonist. (c) Data summary of ATP ligand stimulation of P2XR current in 3 human airway epithelial cell models. n = 4–6 among the 3 airway epithelial cell models. Similar data was obtained using T84 cells (data not shown). (d) Patch-clamp icon illustrates the experimental design, where the pipette (intracellular) solution contains 140 mM potassium gluconate (KGlu) and the bath (extracellular) solution contains 145 mM sodium gluconate (NaGlu). In this design, whole-cell currents are nonselective for cations if the reversal potential is at or near 0 mV. Substitution of Cl– with Glu– eliminates the chance that ATP agonists would stimulate an epithelial Cl– channel, a possibility that is probably based on the preliminary data above. Moreover, Glu– also chelates divalent cations, such as Ca2+ and Mg2+, that may block P2XR channels.