Ionic selectivity of native ATP-activated (P2X) receptor channels in dissociated neurones from rat parasympathetic ganglia.
1. The relative permeability of the native P2X receptor channel to monovalent and divalent inorganic and organic cations was determined from reversal potential measurements of ATP-evoked currents in parasympathetic neurones dissociated from rat submandibular ganglia using the dialysed whole-cell patch clamp technique. 2. The P2X receptor-channel exhibited weak selectivity among the alkali metals with a selectivity sequence of Na(+) > Li(+) > Cs(+) > Rb(+) > K(+), and permeability ratios relative to Cs(+) (P(X)/P(Cs)) ranging from 1.11 to 0.86. 3. The selectivity for the divalent alkaline earth cations was also weak with the sequence Ca(2+) > Sr(2+) > Ba(2+) > Mn(2+) > Mg(2+). ATP-evoked currents were strongly inhibited when the extracellular divalent cation concentration was increased. 4. The calculated permeability ratios of different ammonium cations are higher than those of the alkali metal cations. The permeability sequence obtained for the saturated organic cations is inversely correlated with the size of the cation. The unsaturated organic cations have a higher permeability than that predicted by molecular size. 5. Acidification to pH 6.2 increased the ATP-induced current amplitude twofold, whereas alkalization to 8.2 and 9.2 markedly reduced current amplitude. Cell dialysis with either anti-P2X(2) and/or anti-P2X(4) but not anti-P2X(1) antibodies attenuated the ATP-evoked current amplitude. Taken together, these data are consistent with homomeric and/or heteromeric P2X(2) and P2X(4) receptor subtypes expressed in rat submandibular neurones. 6. The permeability ratios for the series of monovalent organic cations, with the exception of unsaturated cations, were approximately related to the ionic size. The relative permeabilities of the monovalent inoganic and organic cations tested are similar to those reported previously for cloned rat P2X(2) receptors expressed in mammalian cells.
Liu
D M
DM
School of Biomedical Sciences, Department of Physiology and Pharmacology, University of Queensland, Brisbane, Queensland 4072, Australia.
Adams
D J
DJ
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002412:Cations / Q000493:pharmacokinetics; D002586:Cesium / Q000493:pharmacokinetics; D005726:Ganglia, Parasympathetic / Q000166:cytology*; D066298:In Vitro Techniques; D008094:Lithium / Q000493:pharmacokinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000493:pharmacokinetics; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000276:immunology / Q000378:metabolism*; D058476:Receptors, Purinergic P2X2; D058848:Receptors, Purinergic P2X4; D012413:Rubidium / Q000493:pharmacokinetics; D012964:Sodium / Q000493:pharmacokinetics
D000906:Antibodies; D002412:Cations; C546403:P2rx2 protein, rat; C548228:P2rx4 protein, rat; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D058848:Receptors, Purinergic P2X4; D002586:Cesium; D000255:Adenosine Triphosphate; D008094:Lithium; D012964:Sodium; D012413:Rubidium; D011188:Potassium