FIGURE 10.

Electrophysiological characterization of PU02 at mutant S248N, G306I, and L288M/G306S 5-HT₃A receptors expressed in COS-7 cells. A, currents induced by 20 μm 5-HT pulses (solid bars, 45-s interval) in cells expressing S248N, G306I, and L288M/G306S 5-HT₃A mutants were not noticeably reduced by 10 μm PU02. Scale bars, represent 200 pA (vertical) and 5 s (horizontal). Peak amplitudes induced by 20 μm 5-HT in the presence of PU02 were base line-subtracted and normalized to those in the absence of antagonist. B, summation of the effects of PU02 on WT and mutant 5-HT₃A receptor signaling. Data are given as mean ± S.E. values (error bars) based on 5–6 cells on at least three different days and transfections. C, kinetic parameters of mutants compared with WT receptors. Time constants of association and desensitization for currents evoked by 20 μm 5-HT were calculated as described in the legend to Fig. 3. Bars, mean values ± S.E., (n = 5–7). Statistical analysis (one-way analysis of variance with a Dunnett's post-test) indicated a significantly (*, p < 0.05) increased time constant for the desensitization phase of S248N.