Figure 4.

Fast kinetics can account for the lack of time dependence in C₁₀ block of BK channels. (A) An example of macroscopic BK currents before and after the application of 10 and 100 μM C₁₀. Currents were elicited by depolarization of membrane potential to 60 mV from −80 mV under voltage clamp. The smooth line in A is the fit of the control trace to a single exponential function I = I _max (1 − exp(−(t − t ₀)/τ)), where I _max is the maximal current level, t ₀ is the delay in the activation process (Cui et al., 1997), and τ is activation time constant. Values used for the fit are I _max = 4.03 nA, t ₀ = 89 μs, and τ =728 μs. If we assume a two-state activation process: C↔O with opening rate α and closing rate β, then (1/ τ) = α + β, and P _o = α/(α + β). By assuming a P _o of 0.95 at 60 mV we can calculate the values for the forward and backward rates: α = 1,304 s⁻¹ and β = 69 s⁻¹. (B) Gating parameters from A were used for the simulations of currents according to the open-channel block mechanism: C↔O↔B. Block and unblock rate constants are from mean values at 60 mV in Fig. 3 A. Parameters used in the simulations are shown on the top of each trace (solid lines). 10 times the on rate is used in the simulation of 100 μM C₁₀. Dotted lines are simulations when both the block and unblock rates are decreased by 20-fold with the C↔O gating parameters remaining unchanged.