Figure 2.

Effects of BIII 890 CL on Na⁺ currents in cells expressing rbIIA channels. (A) BIII 890 CL-dependent shift in the voltage-dependence of NaIIA WT channel availability. Inactivation curves from a typical cell are shown in the absence or presence of 1 μM or 10 μM BIII 890 CL. Data were normalized to the most negative control value at each concentration and fitted by Boltzmann functions. (Inset) Typical current traces in response to depolarization to 0 mV following a prepulse of −70 mV with and without BIII 890 CL (10 μM). (B) Concentration-response curves for the blockade of WT and IVS6 mutants by BIII 890 CL. Resting WT channels were inhibited with an IC₅₀ value of 18 μM, whereas the concentration for half-maximum block was only 77 nM for inactivated channels. Mutations of the IVS6 region F1764A and Y1771A reduced affinities of inactivated channels to 349 and 619 nM, respectively. (C) Typical example of stimulus-dependent block of NaIIA channels by BIII 890 CL. At a concentration of 1.85 μM, BIII 890 CL induced pronounced activity-dependent block in WT channel-expressing cells. Stimulus-dependent inhibition was largely reduced in IVS6 mutants.