Postsynaptic P2X3‐containing receptors in gustatory nerve fibres mediate responses to all taste qualities in mice. (20th January 2015)

• Record Type: Journal Article
• Authors: Vandenbeuch, Aurelie; Larson, Eric D.; Anderson, Catherine B.; Smith, Steven A.; Ford, Anthony P.; Finger, Thomas E.; Kinnamon, Sue C.
• Is Part Of: Journal of physiology. Volume 593:Number 5(2015:Mar.)
• Page Start: 1113
• Page End: 1125
• Publication Date: 2015-01-20
• Subjects: Physiology -- Periodicals; 612.005
• DOI: 10.1113/jphysiol.2014.281014
• Languages: English
• ISSNs: 0022-3751

Abstract

<abstract abstract-type="main"> <title>Key points</title> <sec id="tjp6507-sec-0010" sec-type="section"> <p> <list id="tjp6507-list-0001" list-type="bullet"> <list-item> <p>Acute inhibition of purinergic receptors with a selective P2X3 antagonist prevents transmission of information from taste buds to sensory nerves.</p> </list-item> <list-item> <p>The P2X3 antagonist has no effect on taste‐evoked release of ATP, confirming the effect is postsynaptic.</p> </list-item> <list-item> <p>The results confirm previous results with P2X2/3 double knockout mice that ATP is required for transmission of all taste qualities, including sour and salty. Previously, ATP was confirmed to be required for bitter, sweet and umami tastes, but was questioned for salty and sour tastes due to pleomorphic deficits in the double knockout mice.</p> </list-item> <list-item> <p>The geniculate ganglion in mouse contains two populations of ganglion cells with different subunit composition of P2X2 and P2X3 receptors making them differently susceptible to pharmacological block and, presumably, desensitization.</p> </list-item> </list> </p> </sec> <sec id="tjp6507-sec-0020" sec-type="section"> <title>Abstract</title> <p>Taste buds release ATP to activate ionotropic purinoceptors composed of P2X2 and P2X3 subunits, present on the taste nerves. Mice with genetic deletion of P2X2 and P2X3 receptors (double knockout mice) lack responses to all taste stimuli presumably due to the absence of ATP‐gated receptors on the afferent nerves. Recent experiments on the double knockout mice showed, however, that their taste buds fail to release ATP, suggesting the possibility of pleiotropic deficits in these global knockouts. To test further the role of postsynaptic P2X receptors in afferent signalling, we used AF‐353, a selective antagonist of P2X3‐containing receptors to inhibit the receptors acutely during taste nerve recording and behaviour. The specificity of AF‐353 for P2X3‐containing receptors was tested by recording Ca<sup>2+</sup> transients to exogenously applied ATP in fura‐2 loaded isolated geniculate ganglion neurons from wild‐type and P2X3 knockout mice. ATP responses were completely inhibited by 10 μ<sc>m</sc> or 100 μ<sc>m</sc> AF‐353, but neither concentration blocked responses in P2X3 single knockout mice wherein the ganglion cells express only P2X2‐containing receptors. Furthermore, AF‐353 had no effect on taste‐evoked ATP release from taste buds. In wild‐type mice, <sc>i.p.</sc> injection of AF‐353 or simple application of the drug directly to the tongue, inhibited taste nerve responses to all taste qualities in a dose‐dependent fashion. A brief access behavioural assay confirmed the electrophysiological results and showed that preference for a synthetic sweetener, SC‐45647, was abolished following <sc>i.p.</sc> injection of AF‐353. These data indicate that activation of P2X3‐containing receptors is required for transmission of all taste qualities.</p> </sec> </abstract>