title: A novel calcium-sensitive potassium conductance is coupled to P2X3 subunit containing receptors in myenteric neurons of guinea pig ileum.
abstract: This study characterized P2X receptors in guinea pig ileum myenteric S neurons (n = 124) in vitro using electrophysiological methods. ATP or alpha,beta-methylene ATP (alpha,beta-mATP), an agonist at P2X(1) and P2X(3) subunit containing receptors, depolarized 103 neurons (85%). Pyridoxal-phosphate-6-azophenyl-2',4' disulfonic acid (10 micromol L(-1)) blocked ATP- and alpha,beta-mATP-induced depolarizations. ATP-induced depolarizations and fast excitatory postsynaptic potentials (fEPSPs) were reduced by trinitrophenyl-ATP (10 micromol L(-1)), an antagonist that can block P2X(3) receptors. Ivermectin (10 micromol L(-1)), a modulator of P2X(4) and P2X(4/6) receptors, had no effect on alpha,beta-mATP-induced depolarizations. In 58% of neurons, the alpha,beta-mATP induced-depolarization was followed by an afterhyperpolarization (AHP) (P2X-AHP). Under voltage clamp, alpha,beta-mATP induced an inward current followed by an outward current which reversed polarity at 0 and -80 mV respectively. The P2X-AHP was reduced in low extracellular Ca(2+) solutions. Blockers of large, intermediate and small conductance Ca(2+)-activated K(+) channels or voltage-gated K(+) channels did not inhibit the P2X-AHP. Half of the neurons exhibiting the P2X-AHP contained nitric oxide synthase (NOS)-immunoreactivity (ir). In summary, NOS-ir S neurons express P2X(3) subunit containing P2X receptors. P2X receptors couple to activation of a Ca(2+)-activated K(+) conductance that mediates an AHP. As P2X receptors contribute to fEPSPs, the P2X-AHP may modulate S neuron excitability during purinergic synaptic transmission.
authors.affiliation: The Neuroscience Program, Department of Pharmacology & Toxicology, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ren
authors.forename: J J
authors.initials: JJ
authors.lastname: Galligan
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006168:Guinea Pigs; D007082:Ileum / Q000294:innervation*; D008297:Male; D009046:Motor Neurons / Q000201:enzymology / Q000502:physiology; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology; D009197:Myenteric Plexus / Q000201:enzymology / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology*; D020239:Receptor Cross-Talk / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*; D058477:Receptors, Purinergic P2X3; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D024681:Potassium Channels, Calcium-Activated; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; C002630:alpha,beta-methyleneadenosine 5'-triphosphate