Figure 5.

Block by dequalinium is state independent. (A) Dose-response relations for dequalinium block in the presence of saturating cGMP (2 mM cGMP, filled squares) and in the presence of subsaturating cGMP (32 μM cGMP, open circles). Data are presented as fraction of block for comparison purposes. The smooth line is a fit with Eq. 1, K_1/2 = 189 nM. (B) Dose-response for cGMP in the absence (filled diamonds) and presence of 400 nM dequalinium (open diamonds). Error bars represent SEM, n = 4 patches. The smooth lines represent fits to the Eq.1 with K_1/2 = 80 μM in the presence of dequalinium K_1/2 = 90 μM in the absence of dequalinium. Dotted line represents normalization of the data obtained in the presence of 400 nM dequalinium to the data obtained in the absence of dequalinium, K_1/2 = 80 μM. (C) Predicted fits with the models shown in Schemes 1–4. Filled and hollow diamonds are from the same data in B. The dashed line represents a fit with Scheme III (pure open channel block), the dotted line represents block only in the closed state (Scheme II, pure closed channel block) and the thin line represents block occurring equally during the closed and open states of the channel with a K_D = 50 nM for both of the conformational states (Scheme IV). The parameter values for these fits were L = 19 and K = 3800 M⁻¹ (in all cases). (D) Block of currents by 250 nM dequalinium in the presence of 2 mM cGMP (left) and in the presence of 20 mM cIMP, a partial agonist of these channels (right). In both cases block was of ∼48%.