P2X2 Subunits Contribute to Fast Synaptic Excitation in Myenteric Neurons of the Mouse Small Intestine

Overview

Journal J Physiol

Specialty Physiology

Date 2003 Aug 26

PMID 12937291

Citations 42

Authors

Jianhua Ren

Xiaochun Bian

Matthew DeVries

Birthe Schnegelsberg

Debra A Cockayne

Anthony P D W Ford

James J Galligan

Affiliations

Soon will be listed here.

Abstract

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. alpha,beta-Methylene ATP (alpha,beta-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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References

Bornstein J, Furness J, Kunze W . Electrophysiological characterization of myenteric neurons: how do classification schemes relate?. J Auton Nerv Syst. 1994; 48(1):1-15. DOI: 10.1016/0165-1838(94)90155-4. View

Lomax A, Sharkey K, Bertrand P, LOW A, Bornstein J, Furness J . Correlation of morphology, electrophysiology and chemistry of neurons in the myenteric plexus of the guinea-pig distal colon. J Auton Nerv Syst. 1999; 76(1):45-61. DOI: 10.1016/s0165-1838(99)00008-9. View

Castelucci P, Robbins H, Poole D, Furness J . The distribution of purine P2X(2) receptors in the guinea-pig enteric nervous system. Histochem Cell Biol. 2002; 117(5):415-22. DOI: 10.1007/s00418-002-0404-4. View

Galligan J, Bertrand P . ATP mediates fast synaptic potentials in enteric neurons. J Neurosci. 1994; 14(12):7563-71. PMC: 6576907. View

Lewis C, Neidhart S, Holy C, North R, Buell G, Surprenant A . Coexpression of P2X2 and P2X3 receptor subunits can account for ATP-gated currents in sensory neurons. Nature. 1995; 377(6548):432-5. DOI: 10.1038/377432a0. View

Bian X, Bertrand P, Bornstein J . Descending inhibitory reflexes involve P2X receptor-mediated transmission from interneurons to motor neurons in guinea-pig ileum. J Physiol. 2000; 528(Pt 3):551-60. PMC: 2270162. DOI: 10.1111/j.1469-7793.2000.00551.x. View

Browning K, Lees G . Myenteric neurons of the rat descending colon: electrophysiological and correlated morphological properties. Neuroscience. 1996; 73(4):1029-47. DOI: 10.1016/0306-4522(96)00118-2. View

Khakh B, Zhou X, Sydes J, Galligan J, Lester H . State-dependent cross-inhibition between transmitter-gated cation channels. Nature. 2000; 406(6794):405-10. DOI: 10.1038/35019066. View

LePard K, Galligan J . Analysis of fast synaptic pathways in myenteric plexus of guinea pig ileum. Am J Physiol. 1999; 276(2):G529-38. DOI: 10.1152/ajpgi.1999.276.2.G529. View

10.

Kim M, Yoo O, Choe S . Molecular assembly of the extracellular domain of P2X2, an ATP-gated ion channel. Biochem Biophys Res Commun. 1997; 240(3):618-22. DOI: 10.1006/bbrc.1997.7713. View

11.

Costa M, Brookes S, Steele P, Gibbins I, Burcher E, Kandiah C . Neurochemical classification of myenteric neurons in the guinea-pig ileum. Neuroscience. 1996; 75(3):949-67. DOI: 10.1016/0306-4522(96)00275-8. View

12.

Kunze W, Furness J, Bertrand P, Bornstein J . Intracellular recording from myenteric neurons of the guinea-pig ileum that respond to stretch. J Physiol. 1998; 506 ( Pt 3):827-42. PMC: 2230753. DOI: 10.1111/j.1469-7793.1998.827bv.x. View

13.

Nurgali K, Furness J, Stebbing M . Analysis of purinergic and cholinergic fast synaptic transmission to identified myenteric neurons. Neuroscience. 2003; 116(2):335-47. DOI: 10.1016/s0306-4522(02)00749-2. View

14.

Johnson P, Shum O, Thornton P, Bornstein J . Evidence that inhibitory motor neurons of the guinea-pig small intestine exhibit fast excitatory synaptic potentials mediated via P2X receptors. Neurosci Lett. 1999; 266(3):169-72. DOI: 10.1016/s0304-3940(99)00275-x. View

15.

Zhou X, Galligan J . P2X purinoceptors in cultured myenteric neurons of guinea-pig small intestine. J Physiol. 1996; 496 ( Pt 3):719-29. PMC: 1160859. DOI: 10.1113/jphysiol.1996.sp021722. View

16.

Hirst G, Holman M, Spence I . Two types of neurones in the myenteric plexus of duodenum in the guinea-pig. J Physiol. 1974; 236(2):303-26. PMC: 1350803. DOI: 10.1113/jphysiol.1974.sp010436. View

17.

Abdu F, Hicks G, Hennig G, Allen J, Grundy D . Somatostatin sst(2) receptors inhibit peristalsis in the rat and mouse jejunum. Am J Physiol Gastrointest Liver Physiol. 2002; 282(4):G624-33. DOI: 10.1152/ajpgi.00354.2001. View

18.

North R, Surprenant A . Pharmacology of cloned P2X receptors. Annu Rev Pharmacol Toxicol. 2000; 40:563-80. DOI: 10.1146/annurev.pharmtox.40.1.563. View

19.

Poole D, Castelucci P, Robbins H, Chiocchetti R, Furness J . The distribution of P2X3 purine receptor subunits in the guinea pig enteric nervous system. Auton Neurosci. 2002; 101(1-2):39-47. DOI: 10.1016/s1566-0702(02)00179-0. View

20.

Zhou X, Galligan J . Non-additive interaction between nicotinic cholinergic and P2X purine receptors in guinea-pig enteric neurons in culture. J Physiol. 1998; 513 ( Pt 3):685-97. PMC: 2231316. DOI: 10.1111/j.1469-7793.1998.685ba.x. View