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P2X purinoceptors in cultured myenteric neurons of guinea-pig small intestine.
J Physiol. 1996 Nov 01; 496 (Pt 3):719-29.JP

Abstract

1. Fast excitatory postsynaptic currents (fEPSCs) and responses to exogenously applied purinoceptor agonists were studied in primary cultures of myenteric neurons from guinea-pig small intestine. Whole-cell and outside-out configurations of the patch clamp technique were used. Hexamethonium (100 microM) partly inhibited fEPSCs in 28% of neurons. Hexamethonium-resistant fEPSCs were inhibited by 97 +/- 2% by the P2X receptor antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 10 microM). 2. ATP caused two types of inward currents. In 92% of neurons (n = 123), ATP caused a slowly desensitizing current that declined with a double exponential time course (tau 1 = 7.1 +/- 2.0 s; tau 2 = 57 +/- 7.4 s, n = 4). The rank order potency for purinoceptor agonists in these neurons was ATP > 2-methylthio-ATP (2-MeSATP) > > alpha, beta-methylene ATP (alpha, beta-me ATP) > beta, gamma-meATP > ADP. The EC50 values for ATP and 2-MeSATP were 40 and 65 microM, respectively. alpha, beta-MeATP acted as a partial agonist at these receptors. In 8% of neurons (n = 11), ATP-induced currents desensitized rapidly with a double exponential time course (tau 1 = 0.13 +/- 0.015 s; tau 2 = 2.2 +/- 1.3 s, n = 4); alpha, beta-meATP caused similar responses in these cells. Both types of ATP-induced current were associated with an increased conductance and an inwardly rectifying I-V relationship (Erev = 10 mV). Halving [Na+]o shifted the reversal potential of ATP currents by -22 +/- 6 mV. 3. ATP activated single channel currents in outside-out patches. The single channel I-V relationship was linear between -120 and 60 mV (Erev approximately 0 mV). Single channel conductance between -100 and -60 mV was 25 +/- 2 pS. Single channel open probability was voltage dependent and decreased from 0.05 +/- 0.01 at -100 mV to 0.007 +/- 0.002 at +40 mV. 4. These data show that P2X purinoceptors mediate some fEPSCs in cultured myenteric neurons. Myenteric neurons express the fast-desensitizing alpha, beta-me ATP-sensitive subtype of P2X receptor that has the properties of cloned P2X1 receptors and is similar to native receptors in smooth muscle cells. Myenteric neurons also express a P2X receptor that desensitized slowly and was alpha, beta-meATP-insensitive. This receptor has the properties of cloned P2X2 or P2X5 receptors and is similar to native receptors found in PC-12 cells and superior cervical ganglion neurons. The known distribution of P2X2 and P2X5 receptors suggests that myenteric neurons are likely to express predominantly P2X2 receptors.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Michigan State University, East Lansing, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8930839

Citation

Zhou, X, and J J. Galligan. "P2X Purinoceptors in Cultured Myenteric Neurons of Guinea-pig Small Intestine." The Journal of Physiology, vol. 496 (Pt 3), 1996, pp. 719-29.
Zhou X, Galligan JJ. P2X purinoceptors in cultured myenteric neurons of guinea-pig small intestine. J Physiol (Lond). 1996;496 (Pt 3):719-29.
Zhou, X., & Galligan, J. J. (1996). P2X purinoceptors in cultured myenteric neurons of guinea-pig small intestine. The Journal of Physiology, 496 (Pt 3), 719-29.
Zhou X, Galligan JJ. P2X Purinoceptors in Cultured Myenteric Neurons of Guinea-pig Small Intestine. J Physiol (Lond). 1996 Nov 1;496 (Pt 3):719-29. PubMed PMID: 8930839.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - P2X purinoceptors in cultured myenteric neurons of guinea-pig small intestine. AU - Zhou,X, AU - Galligan,J J, PY - 1996/11/1/pubmed PY - 1996/11/1/medline PY - 1996/11/1/entrez SP - 719 EP - 29 JF - The Journal of physiology JO - J. Physiol. (Lond.) VL - 496 (Pt 3) N2 - 1. Fast excitatory postsynaptic currents (fEPSCs) and responses to exogenously applied purinoceptor agonists were studied in primary cultures of myenteric neurons from guinea-pig small intestine. Whole-cell and outside-out configurations of the patch clamp technique were used. Hexamethonium (100 microM) partly inhibited fEPSCs in 28% of neurons. Hexamethonium-resistant fEPSCs were inhibited by 97 +/- 2% by the P2X receptor antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 10 microM). 2. ATP caused two types of inward currents. In 92% of neurons (n = 123), ATP caused a slowly desensitizing current that declined with a double exponential time course (tau 1 = 7.1 +/- 2.0 s; tau 2 = 57 +/- 7.4 s, n = 4). The rank order potency for purinoceptor agonists in these neurons was ATP > 2-methylthio-ATP (2-MeSATP) > > alpha, beta-methylene ATP (alpha, beta-me ATP) > beta, gamma-meATP > ADP. The EC50 values for ATP and 2-MeSATP were 40 and 65 microM, respectively. alpha, beta-MeATP acted as a partial agonist at these receptors. In 8% of neurons (n = 11), ATP-induced currents desensitized rapidly with a double exponential time course (tau 1 = 0.13 +/- 0.015 s; tau 2 = 2.2 +/- 1.3 s, n = 4); alpha, beta-meATP caused similar responses in these cells. Both types of ATP-induced current were associated with an increased conductance and an inwardly rectifying I-V relationship (Erev = 10 mV). Halving [Na+]o shifted the reversal potential of ATP currents by -22 +/- 6 mV. 3. ATP activated single channel currents in outside-out patches. The single channel I-V relationship was linear between -120 and 60 mV (Erev approximately 0 mV). Single channel conductance between -100 and -60 mV was 25 +/- 2 pS. Single channel open probability was voltage dependent and decreased from 0.05 +/- 0.01 at -100 mV to 0.007 +/- 0.002 at +40 mV. 4. These data show that P2X purinoceptors mediate some fEPSCs in cultured myenteric neurons. Myenteric neurons express the fast-desensitizing alpha, beta-me ATP-sensitive subtype of P2X receptor that has the properties of cloned P2X1 receptors and is similar to native receptors in smooth muscle cells. Myenteric neurons also express a P2X receptor that desensitized slowly and was alpha, beta-meATP-insensitive. This receptor has the properties of cloned P2X2 or P2X5 receptors and is similar to native receptors found in PC-12 cells and superior cervical ganglion neurons. The known distribution of P2X2 and P2X5 receptors suggests that myenteric neurons are likely to express predominantly P2X2 receptors. SN - 0022-3751 UR - https://www.unboundmedicine.com/medline/citation/8930839/P2X_purinoceptors_in_cultured_myenteric_neurons_of_guinea_pig_small_intestine_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3751&date=1996&volume=496&spage=719 DB - PRIME DP - Unbound Medicine ER -