The amplitude and time constant of the decay of the cocaine-induced current are concentration dependent. (A) Representative currents from the same cell evoked by rapid application of 30 µM 5-HT (upper panel) or 100 µM cocaine (lower panel), respectively. The currents were recorded at 0 mV and in the presence of 152 mM intracellular Na+. (B) Comparison of the amplitudes of the 5-HT (blue circles) and the cocaine-induced peak current (red circles). The lines connect measurements from the same cell: 5-HT: −18.8 ± 9.1 pA; cocaine: −6.0 ± 2.4 pA; n = 8; p=0.008, Wilcoxon test. (C) Representative currents elicited by 3 µM (black), 10 µM (orange), 30 µM (green), 100 µM (blue) and 300 µM (magenta) cocaine, respectively. The depicted currents were recorded from the same cell. (D) Rate of current decay as a function of cocaine concentration. The line is a linear fit to the data points (slope: 2.9*105 ± 0.3*105 Mol−1s−1; n = 7). Data are mean ± SD. (E) In the absence of Na+, 100 µM cocaine failed to induce a peak current. Shown are representative traces in the presence of 150 mM extracellular NMDG+ (upper panel) and 150 mM extracellular Na+ (lower panel), respectively. The depicted traces were recorded from the same cell. The absence of the cocaine-induced current in the presence of NMDG+ was confirmed in seven independent experiments. (F) Representative currents in the presence of 150 mM extracellular MES- (upper panel) and 150 mM extracellular Cl- (lower panel), respectively. (G) The amplitude of the cocaine-induced current peak was −7.7 ± 1.7 pA (n = 9) and −3.1 ± 1.0 pA (n = 15) in the presence and absence of Cl-, respectively (p<0.0001; Mann-Whitney U-test). Source files are available in Figure 1—source data 1.