Figure 4.
Effect of high concentrations of suramin. A, hypothetical model (derived from Fig. 1F) in which both Cl− (green) and suramin (red) could access the open pore via one “primary” portal (from the left as shown), whereas a “secondary” portal (from the right) allows access by Cl− but not suramin (for example, because of restricted dimensions) (see “Results”). B, example macroscopic current–voltage relationships for the weakly suramin-sensitive mutant K370Q (left panel) and the strongly suramin-sensitive mutant K1041Q (right panel) in inside-out patches. In both cases, current was recorded before (control, black) and after (red) addition of 1 mm suramin to the intracellular solution. C, mean fraction of control current remaining after addition of different concentrations of suramin to the intracellular solution for the different channel variants indicated. The mean data have been fitted as described under “Experimental Procedures” (Equation 2) with the following parameters: wildtype Kd 11.6 μm, nh 0.87, rf 0.047; R303Q Kd 32.3 μm, nh 0.93, rf 0.06; K370Q Kd 39.5 μm, nh 1.10, rf 0.034; and K1041Q Kd 2.0 μm, nh 1.19, rf 0.060. The asterisk indicates concentrations at which mutations showed a significant difference from wildtype (p < 0.05). At high concentrations (1–10 mm), none of the mutants studied showed a significant difference from wildtype. The means of data from 4–10 patches are shown.