Simulation of Kv2.1 and Kv2.1/Kv6.4 gating currents.

(A) Scheme depicting the simplified model in which the activation of each subunit was modeled with a single closed (C) to activated (A) transition with an exponential voltage-dependence of the microscopic rate constants with parameters as detailed in panel B. Once all four subunits are in the A state, transition to the open (O) state occur in a final (voltage independent) step (B) Markov model used for the simulation of Kv2.1 and Kv2.1/Kv6.4 gating currents. In case of Kv2.1 homotetramers, C* = C, A* = A, and α* = α, and β* = β. For the heterotetramer C* and A* represent the Kv6.4 subunit in the Kv2.1/Kv6.4 in 3∶1 stoichiometry with distinct parameters for α* and β*. The values used to simulate the gating currents with this model are given in the box below. For further details on these models see the materials and methods section. (C) Simulated I_Q gating currents at different potentials for the Kv2.1 homotetramer (left) and Kv2.1/Kv6.4 heterotetramer (right) using the model shown in panel a. Note the crossing at −50 mV for the Kv2.1/Kv6.4 heterotetrameric channel. (D) Q–V curves for Kv2.1 (circle) and Kv2.1/Kv6.4 (triangle) obtained by integrating the simulated I_Q shown in panel B and fitted with Boltzmann function. (E) Voltage-dependence of the weighted time constants of I_Q of Kv2.1 (circle) and Kv2.1/Kv6.4 (triangle) channels obtained by fitting the I_Q decay from the simulated I_Q shown in panel C. Note the negative component in both the Kv2.1+Kv6.4 Q–V curve and I_Q kinetics which correspond well with the experimental data in figure 1.