FIGURE 1.

Principal blocking mechanisms of a noninactivating channel. (A) Kinetic schemes. C and O denote closed and open states of the unbound channel, CB and OB closed and open (but nonconducting) states of the local anesthetic bound channel; α, β, κ, and λ denote rate constants and c the local anesthetic concentration. (B) Computed time courses of the open probability for the different schemes. Calculated for K_d concentration from Eqs. 3–5, assuming V = +60 mV and using parameter values in Table 1 (Shaker) for fast, intermediate, and slow blocking rates (κ = λ = 1, 0.1, and 0.01 ms⁻¹, respectively). (C) Computed time courses of the open probability for the different schemes at concentrations 0.3 × K_d, K_d, and 3 × K_d, assuming intermediate blocking rates (κ = 0.1 and λ = 0.1 ms⁻¹).