Figure 1. Working models: distinct trap-door scenarios in Shaker and Kv4.1 channels.

(a) Cartoon representation of activation and P/C-type inactivation mechanisms in Shaker Kv channels (Model I). For clarity, only two opposing subunits of a Kv channel tetramer are represented in the cartoons. Top and bottom are the extracellular and intracellular sides of the channel, respectively. Voltage sensors (black rod with plus signs) undergo a voltage-dependent conformational change that controls the state of the intracellular activation gate (red bars). S4–S5 linkers (black elbows) interact with the activation gate to transmit the movement of the voltage sensors to the activation gate. Once this gate opens, the Kv channel allows transmembrane K⁺ flow (green circles) driven by an electrochemical potential. Closing of the activation gate traps the QA ion as shown by Holmgren et al.⁴. However, inactivation occurs at the external selectivity filter, which does not close the internal activation gate and, therefore, there is no QA ion trapping by inactivation. (b) Cartoon representation of a putative activation-inactivation mechanism in Kv4.1 channels (Model II). Note that closing of the internal gate traps the QA ion. Additionally, disconnecting the voltage sensors from the activation gate inactivates the channel as proposed by Shin et al.³⁷ and maintains the trapped state. The dashed perimeters enclose common pathways in Models I and II.