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This Article Full Text Full Text (PDF) All Versions of this Article: 552/3/809    most recent jphysiol.2003.047944v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ren, J. Articles by Galligan, J. J. Search for Related Content PubMed PubMed Citation Articles by Ren, J. Articles by Galligan, J. J.

P2X₂ subunits contribute to fast synaptic excitation in myenteric neurons of the mouse small intestine

Jianhua Ren†, Xiaochun Bian*†, Matthew DeVries*, Birthe Schnegelsberg‡, Debra A. Cockayne‡, Anthony P. D. W. Ford‡ and James J. Galligan*†

P2X receptors are ATP-gated cation channels composed of one or more of seven different subunits. ATP acts at P2X receptors to contribute to fast excitatory postsynaptic potentials (fEPSPs) in myenteric neurons but the subunit composition of enteric P2X receptors is unknown. These studies used tissues from P2X₂ wild-type (P2X₂^+/+) and P2X₂ gene knockout (P2X₂^-/-) mice to investigate the role of this subunit in enteric neurotransmission. Intracellular electrophysiological methods were used to record synaptic and drug-induced responses from ileal myenteric neurons in vitro. Drug-induced longitudinal muscle contractions and peristaltic contractions of ileal segments were also studied in vitro. Gastrointestinal transit was measured as the progression in 30 min of a liquid radioactive marker administered by gavage to fasted mice. RT-PCR analysis of mRNA from intestinal tissues and data from immunohistochemical studies verified P2X₂ gene deletion. The fEPSPs recorded from S neurons in tissues from P2X₂^+/+ mice were reduced by mecamylamine (nicotinic cholinergic receptor antagonist) and PPADS (P2X receptor antagonist). The fEPSPs recorded from S neurons from P2X₂^-/- mice were unaffected by PPADS but were blocked by mecamylamine. ATP depolarized S and AH neurons from P2X₂^+/+ mice. ATP depolarized AH but not S neurons from P2X₂^-/- mice. ,-Methylene ATP (,-mATP)(an agonist at P2X₃ subunit-containing receptors) did not depolarize S neurons but it did depolarize AH neurons in P2X₂^+/+ and P2X₂^-/- mice. Peristalsis was inhibited in ileal segments from P2X₂^-/- mice but longitudinal muscle contractions caused by nicotine and bethanechol were similar in segments from P2X₂^+/+ and P2X₂^-/- mice. Gastrointestinal transit was similar in P2X₂^+/+ and P2X₂^-/- mice. It is concluded that P2X₂ homomeric receptors contribute to fEPSPs in neural pathways underlying peristalsis studied in vitro.

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