MPI Campus Seminar: Molecular Simulations of Ion Permeation, Selectivity and Gating in Potassium Channels

Potassium (K+) channels play a pivotal role in many biological functions, such as formation of the membrane potential and mediating electrical signals in excitable cells (for example neurons or cardiac cells). Structural and functional studies revealed main features of these channels, including rapid and selective potassium ion permeation through a narrow selectivity filter (SF) and channel opening and closing at the activation gate, and distinct gating at the SF, termed C-type inactivation. Despite such insights, the molecular mechanisms of permeation and gating phenomena remain largely unknown, and are further complicated by differences exhibited in numerous, structurally distinct members of the potassium channel family.
Nowadays, Molecular Dynamics (MD) simulations allow studying ion channels in ‘real time’, by following thousands of individual ion permeation events on the atomistic scale, that directly correspond to experimentally measured ionic currents in electrophysiological recordings. Here, we will show MD simulations of several potassium channels, all sharing nearly identical SFs. Our simulations show that all studied K+ channels achieve their high potassium permeation rates by stripping potassium ions off their hydration shells. Simultaneously, the strong interactions of potassium ions in the SF efficiently exclude any sodium ions from permeation, due to their higher dehydration penalty. Moreover, we will present simulation data that show permeation rate variations as a function of the SF width, explaining channel gating at the molecular level.

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