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P2X4 subunits are part of P2X native channels in murine myenteric neurons.
Eur J Pharmacol 2013; 709(1-3):93-102EJ

Abstract

The aim of the present study was to investigate if P2X4 receptors are expressed in murine myenteric neurons and if these receptors contribute to form functional channels in the neuronal membrane by using molecular and electrophysiological techniques. The whole-cell recording technique was used to measure membrane currents induced by ATP (I(ATP)) in myenteric neurons. Compared with recombinant P2X4 receptor-channels (reported by others in a previous study), native myenteric P2X receptors have a relative lower sensitivity for ATP (EC₅₀=102 µM) and α,β methylene ATP (not effect at 30 or 100 µM). BzATP was a weak agonist for native P2X receptors. KN-62 had no effect on myenteric P2X channels whereas PPADS (IC₅₀=0.54 µM) or suramin (IC₅₀=134 µM) were more potent antagonists than on P2X4 homomeric channels. I(ATP) were potentiated by ivermectin (effect that is specific on P2X4 receptors) and zinc. Western blotting shows the presence of P2X4 protein and RT-PCR the corresponding mRNA transcript in the small intestine. Immunoreactivity for P2X4 receptors was found in most myenteric neurons in culture. Single-cell RT-PCR shows the presence of P2X4 mRNA in 90% of myenteric neurons. Our results indicate that P2X4 receptors are expressed in the majority of myenteric neurons, contribute to the membrane currents activated by ATP, and because most properties of I(ATP) does not correspond to P2X4 homomeric channels it is proposed that P2X4 are forming heteromeric channels in these neurons. P2X4 subunits have a widespread distribution within the myenteric plexus and would be expected to play an important role in cell signaling.

Authors+Show Affiliations

División de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica, San Luis Potosí, SLP 78216, Mexico.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23567069

Citation

Nieto-Pescador, María G., et al. "P2X4 Subunits Are Part of P2X Native Channels in Murine Myenteric Neurons." European Journal of Pharmacology, vol. 709, no. 1-3, 2013, pp. 93-102.
Nieto-Pescador MG, Guerrero-Alba R, Valdez-Morales E, et al. P2X4 subunits are part of P2X native channels in murine myenteric neurons. Eur J Pharmacol. 2013;709(1-3):93-102.
Nieto-Pescador, M. G., Guerrero-Alba, R., Valdez-Morales, E., Espinosa-Luna, R., Jiménez-Vargas, N., Liñan-Rico Andrómeda, A., ... Barajas-López, C. (2013). P2X4 subunits are part of P2X native channels in murine myenteric neurons. European Journal of Pharmacology, 709(1-3), pp. 93-102. doi:10.1016/j.ejphar.2013.03.045.
Nieto-Pescador MG, et al. P2X4 Subunits Are Part of P2X Native Channels in Murine Myenteric Neurons. Eur J Pharmacol. 2013 Jun 5;709(1-3):93-102. PubMed PMID: 23567069.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - P2X4 subunits are part of P2X native channels in murine myenteric neurons. AU - Nieto-Pescador,María G, AU - Guerrero-Alba,Raquel, AU - Valdez-Morales,Eduardo, AU - Espinosa-Luna,Rosa, AU - Jiménez-Vargas,Nestor, AU - Liñan-Rico Andrómeda,Andrómeda, AU - Ramos-Lomas,Telma L, AU - Díaz-Hernández Verónica,Verónica, AU - Montaño,Luis M, AU - Barajas-López,Carlos, Y1 - 2013/04/06/ PY - 2012/10/02/received PY - 2013/03/27/revised PY - 2013/03/28/accepted PY - 2013/4/10/entrez PY - 2013/4/10/pubmed PY - 2013/12/16/medline SP - 93 EP - 102 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 709 IS - 1-3 N2 - The aim of the present study was to investigate if P2X4 receptors are expressed in murine myenteric neurons and if these receptors contribute to form functional channels in the neuronal membrane by using molecular and electrophysiological techniques. The whole-cell recording technique was used to measure membrane currents induced by ATP (I(ATP)) in myenteric neurons. Compared with recombinant P2X4 receptor-channels (reported by others in a previous study), native myenteric P2X receptors have a relative lower sensitivity for ATP (EC₅₀=102 µM) and α,β methylene ATP (not effect at 30 or 100 µM). BzATP was a weak agonist for native P2X receptors. KN-62 had no effect on myenteric P2X channels whereas PPADS (IC₅₀=0.54 µM) or suramin (IC₅₀=134 µM) were more potent antagonists than on P2X4 homomeric channels. I(ATP) were potentiated by ivermectin (effect that is specific on P2X4 receptors) and zinc. Western blotting shows the presence of P2X4 protein and RT-PCR the corresponding mRNA transcript in the small intestine. Immunoreactivity for P2X4 receptors was found in most myenteric neurons in culture. Single-cell RT-PCR shows the presence of P2X4 mRNA in 90% of myenteric neurons. Our results indicate that P2X4 receptors are expressed in the majority of myenteric neurons, contribute to the membrane currents activated by ATP, and because most properties of I(ATP) does not correspond to P2X4 homomeric channels it is proposed that P2X4 are forming heteromeric channels in these neurons. P2X4 subunits have a widespread distribution within the myenteric plexus and would be expected to play an important role in cell signaling. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/23567069/P2X4_subunits_are_part_of_P2X_native_channels_in_murine_myenteric_neurons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(13)00263-X DB - PRIME DP - Unbound Medicine ER -