Markov model of KCNQ1 current. (A) KCNQ1 Markov model. Energy landscapes of four subunits determine channel residency in the permissive state, from which the channel can open. All four subunits in the permissive state (left of dotted white line) enable channel transitions to the open states (O1–O5). Inactivated state, I, is only accessible from O5. Flickery blocked state is available from any conformation. (B) Single-channel currents. Traces show random nature of opening. (C) Macroscopic KCNQ1 current is the sum of 1,000 single channels. A hook (arrow in inset that enlarges tail current), characteristic of KCNQ1, is observed upon repolarization and is caused by channel recovery from inactivation. Modified from Silva et al. (2009).