Ionotropic P2X purinoreceptors mediate synaptic transmission in rat pyramidal neurones of layer II/III of somato-sensory cortex.
Fast P2X receptor-mediated excitatory postsynaptic current (EPSC) was identified in pyramidal neurones of layer II/III of somato-sensory cortex in acutely isolated slices obtained from the brain of 17- to 22-day-old rats. The EPSCs were elicited by electrical stimulation of vertical axons originating from layer IV-VI neurones at 0.1 Hz in the presence of bicuculline. When the glutamatergic EPSC was blocked by saturating concentrations of glutamate receptor inhibitors 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo-[f]-quinoxaline-7-sulphonamide (NBQX) and D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5), a small EPSC component was recorded from 90 % of neurones tested. This residual EPSC was not affected by selective blockers of nicotinic (hexamethonium) or serotonin (N-(1-azabicyclo-[2.2.2]oct-3-yl)-6-chloro-4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-8-carboxamide hydrochloride, Y-25130) receptors, but it was reversibly inhibited by the antagonists of P2X receptors NF023 (8,8'-[carbonylbis(imino-3,1-phenylenecarbonylimino)]bis-1,3,5-naphthalene-trisulphonic acid), NF279 (8,8'-[carbonylbis (imino-4,1-phenylenecarbonylimino-4,1-phenylenecarbonylimino)]bis-1,3,5-naphthalene-trisulphonic acid) and PPADS (pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid). Application of ATP (10 microM) or alpha,beta-methylene ATP (10 microM) to pyramidal neurones, acutely isolated from cortical slices, evoked inward currents (30 to 200 pA) in 65 % of cells tested. The relative calcium/caesium permeability (P(Ca)/P(Cs)) of P2X receptors was 12.3 as estimated from the reversal potential of ATP-induced current measured at different extracellular calcium concentrations. We concluded that P2X purinoreceptors are activated during synaptic transmission in neocortex.
School of Biological Sciences, University of Manchester, 1.124 Stopford Building, Oxford Road, Manchester M13 9PT, UK.
Y
Y
Pankratov
U
U
Lalo
O
O
Krishtal
A
A
Verkhratsky
D015763:2-Amino-5-phosphonovalerate; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D013003:Somatosensory Cortex / Q000166:cytology / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018048:Receptors, Purinergic P2; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D015763:2-Amino-5-phosphonovalerate; D000255:Adenosine Triphosphate; D001640:Bicuculline