Figure 4.

Permeability to organic cations. A, E_rev recorded under bi-ionic conditions (130 mm Cs_in) with a series of organic cations of increasing size (all 130 mm), dimethylammonium (2MA), trimethylammonium (3MA), tetramethylammonium (4MA), and NMDG. Mean ± SD; n = 3–7 cells per data point. B, Relative permeabilities (P_x:P_Cs; Eq. 1 in Table 1) derived from data in A, plotted against cation diameter. The data have been fitted with an excluded volume equation (Eq. 3). On the assumption that relative permeability is determined by size alone, this can be used to derive the effective diameter of the pore. The data for the wild-type channel (WT is trpl mutant) have been fitted both with (solid curve) and without (dotted curve) the data point for dimethylammonium (see Results). The inset shows the effective diameter of the pore derived from these fits: the wild-type pore diameter was estimated at 8.6 Å when the dimethylammonium data point was included in the fit but only 7.4 Å when it was excluded (dotted line). The estimated TRP^D621E pore diameter (6.6 Å) was substantially smaller than either of these estimates, whereas values for TRP^D621N and TRP^D621G fell between the two wild-type estimates.