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Purinergic signalling in the medullary mechanisms of respiratory control in the rat: respiratory neurones express the P2X(2) receptor subunit

Gourine, AV; Atkinson, L; Deuchars, J; Spyer, KM; (2003) Purinergic signalling in the medullary mechanisms of respiratory control in the rat: respiratory neurones express the P2X(2) receptor subunit. J PHYSIOL-LONDON , 552 (1) 197 - 211. 10.1113/jphysiol.2003.045294.

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Abstract

ATP is involved in central respiratory control and may mediate changes in the activity of medullary respiratory neurones during hypercapnia, thus playing an important role in central chemoreception. The main objective of this study was to explore further the role of ATP-mediated signalling in respiratory control and central chemoreception by characterising the profile of the P2X receptors expressed by physiologically identified respiratory neurones. In particular we determined whether respiratory neurones in the rostral ventrolateral medulla (VLM) express P2X(2) receptor subunits of the ATP-gated ion channel, since ATP currents evoked at recombinant P2X(2) receptors are potentiated by lowering extracellular pH. Experiments were performed on anaesthetised (pentobarbitone sodium 60 mg kg(-1) i.p., then 10 mg kg(-1) i.v. as required), gallamine-triethiodide-treated (10 mg kg(-1) i.v., then 2-4 mg kg(-1) h(-1) i.v.) and artificially ventilated rats. The VLM respiratory neurones were classified according to the timing of their discharge pattern in relation to that of the phrenic nerve and by the exclusion of pump cells from the study population; these were labelled with Neurobiotin using the juxtacellular method, and visualised with fluorescence microscopy. It was found that a substantial proportion of the VLM respiratory neurones express the P2X(2) receptor subunit. P2X(2) receptor subunit immunoreactivity was detected in similar to50% (six out of 12) of expiratory neurones and in similar to20% (two out of 11) of neurones with inspiratory-related discharge (pre-inspiratory and inspiratory). In contrast, no Neurobiotin-labelled VLM respiratory neurones (n = 19) were detectably immunoreactive for the P2X(1) receptor subunit. Microionophoretic application of ATP (0.2 m, 20-80 nA for 40 s) increased the activity of similar to80% (13 out of 16) of expiratory neurones and of similar to30% (five out of 18) of VLM neurones with inspiratory-related discharge. These effects were abolished by the P2 receptor blocker suramin (0.02 m, 80 nA), which also reduced the baseline firing in some expiratory neurones. These data indicate that modulation of P2X(2) receptor function, such as that evoked by acidification of the extracellular environment during hypercapnia, may contribute to the changes in activity of the VLM respiratory neurones that express these receptors.

Type:Article
Title:Purinergic signalling in the medullary mechanisms of respiratory control in the rat: respiratory neurones express the P2X(2) receptor subunit
DOI:10.1113/jphysiol.2003.045294
Keywords:ROSTRAL VENTROLATERAL MEDULLA, CENTRAL CO2 CHEMORECEPTION, BRAIN-STEM, RHYTHM GENERATION, EXTRACELLULAR PH, IN-VITRO, BOTZINGER NEURONS, ATP, VIVO, SENSITIVITY
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Neuroscience, Physiology and Pharmacology

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