P2X receptors are a subfamily of purinoceptors that are activated by extracellular nucleotides, forming Ca2+ permeable non-selective cation channels. We have studied the pharmacological profile of a Ca²⁺ permeable ATP activated current in isolated single proximal tubule cells and found an agonist potency profile of ATP=α,β-MeATP>2-MeSATP>BzATP (Davies & Robson). To further characterise the properties of this current the monovalent cation and cation:anion selectivity of the current has been investigated.Rana Temporaria frogs were killed humanely by cervical dislocation and single proximal tubule cells were isolated from frog kidneys by enzyme digestion (Hunter, 1989). Standard patch clamp techniques were used to gain whole cell patches via the basolateral membrane. The pipette contained (in mM): 100 NaCl, 2 MgCl2, 0.5 EGTA and 10 HEPES (NaOH). The Na+: Clselectivity of the ATP activated current was investigated by measuring the reversal potential (Vrev) of the current activated by 2mM ATP in a high NaCl frog Ringer (containing in mM: 100 NaCl, 0.1 MgCl2, 0.5 CaCl2 and 10 HEPES (NaOH)) and then in a low NaCl frog Ringer, NaCl reduced five-fold, osmolality maintained by addition of mannitol. Monovalent cation selectivity of the ATP activated current was investigated by measuring the reversal potential of the 2mM ATP activated current in high a) NaCl Ringer b) RbCl Ringer c) CsCl Ringer d) LiCl Ringer or e) NMDGCl Ringer. Whole cell potential was held at -40mV and was then stepped from -100mV to +20mV. The reversal potentials of the ATP activated currents in each solution were compared within experiment groups. Change in Vrev was used to calculate the selectivity ratios of the ions using the Goldman equation. Data are expressed as mean +/- S.E.M. Statistical analysis was performed using ANOVAs and significance was assumed at the 5% level.The change in Vrev of the ATP activated current from the high NaCl solution to the low NaCl solution was -24.50 +/- 2.28 mV (n=11). This corresponds to a Na+: Cl- selectivity ratio of 14: 1. The change in Vrev of the ATP activated current from NaCl to RbCl, CsCl, LiCl and NMCGCl was 9.73 +/- 3.01 mV (n=10), 4.55 +/- 0.82 mV (n=9), 6.53 +/- 2.71 mV (n=9) and -19.51 +/- 2.47 mV (n=10), respectively. This gave a selectivity ratio, Na+:Rb+:Cs+:Li+:NMDG+, of 1: 1.59: 1.21: 1.37: 0.47. Therefore the channel is selective for cations over anions and has a monovalent cation selectivity profile of Rb+=Cs+=Li+>Na+>NMDG+. These data are consistent with the ATP-activated current being attributable to a P2X receptor.