Extracellular ATP dose-dependently potentiates GABA
R-mediated currents in neurons. Whole-cell patch-clamp recording were made from rat cultured hippocampal neurons. GABAAR-mediated currents were evoked by a pulse pressure ejection of GABA (100 μM) from the tip of a pipette positioned close to the neurons under recording. A, Bath application of ATP (4 mM) reversibly potentiates GABA currents (ATP; 171.9 ± 13.8% of the Control; P < 0.01; n = 7) and the potentiated currents remained sensitive to bicuculline (10 μM) blockade (ATP + bicuculline). Representative current traces were taken 5 min before and after drug applications or washout as indicated. B, The dose-response curve showing the dose-dependent potentiation of GABA currents by various concentrations of ATP (n = 8). Each data point represents the mean ± SEM of GABA currents (normalized to Control) at the indicated ATP concentrations. The solid line is the best fit of the data to the Hill equation, which yields a mean EC50 of 2.1 ± 0.3 mM and H of 1.66. C, ATP increases the amplitude of GABA currents without altering their reversal potential. Left: Superimposed individual traces of currents evoked by GABA (10 μM) in the absence (Control) and presence of ATP (4 mM) at different holding potentials from -60 to +60 mV with a step of 20 mV. Right: current-voltage (I-V) relationships constructed from the data shown in the Left.