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 monovale nt and divalent inorganic and organic cations was determined from reversal potential measurements of ATP-evoked currents in parasympathetic neurones d issociated from rat submandibular ganglia using the dialysed whole-cell pat ch clamp technique. 2. The P2X receptor-channel exhibited weak selectivity among the alkali met als with a selectivity sequence of Na+ > Li+ > Cs+ > Rb+ > K+, and permeabi lity 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 wi th the sequence Ca2+ > Sr2+ > Ba2+ > Mn2+ > Mg2+. ATP-evoked currents were strongly inhibited when the extracellular divalent cation concentration was increased. 4, The calculated permeability ratios of different ammonium cations are hig her than those of the alkali metal cations. The permeability sequence obtai ned 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 twof old, 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, wi th the exception of unsaturated cations, were approximately related to the ionic size. The relative permeabilities of the monovalent inoganic and orga nic cations tested are similar to those reported previously for cloned rat P2X2 receptors expressed in mammalian cells.