Ion channels and ion selectivity

Abstract

Specific macromolecular transport systems, ion channels and pumps, provide the pathways to facilitate and control the passage of ions across the lipid membrane. Ion channels provide energetically favorable passage for ions to diffuse rapidly and passively according to their electrochemical potential. Selective ion channels are essential for the excitability of biological membranes: the action potential is a transient phenomenon that reflects the rapid opening and closing of voltage-dependent Na+-selective and K+-selective channels. One of the most critical functional aspects of K+ channels is their ability to remain highly selective for K+ over Na+ while allowing high-throughput ion conduction at a rate close to the diffusion limit. Permeation through the K+ channel selectivity filter is believed to proceed as a “knock-on” mechanism in which 2–3 K+ ions interspersed by water molecules move in single file. Permeation through the comparatively wider and less selective Na+ channels also proceeds via a loosely coupled knock-on mechanism, although the ions do not need to be fully dehydrated. While simple structural concepts are often invoked to rationalize the mechanism of ion selectivity, a deeper analysis shows that subtle effects play an important role in these flexible dynamical structures.

Challenges and advances in atomistic simulations of potassium and sodium ion channel gating and permeation

“…The SFs of some K + channels are responsible for the channels' 10,000-fold preference for K + over Na + (not explicitly discussed in this paper; see Roux, 2017 for a recent review) and can facilitate the flux of 10 8 K + ions per second (Hille, 2001) across a membrane. The SFs of such K + channels as KcsA, K V AP and K V 1.2 are narrow passageways that are lined with the backbone atoms of the highly conserved TVGYG amino acid sequence (Doyle et al 1998;Lee et al 2005;Long et al 2005a).…”

The structure of a potassium-selective ion channel reveals a hydrophobic gate regulating ion permeation

“…Ion channels are a physiologically essential class of proteins that are ubiquitously expressed in organisms ranging from bacteria to human beings (Roux, 2017). They reside within cellular membranes and the lipid bilayers that segment cellular compartments, where they provide a barrier to the passage of components, which is vital for an array of physiological processes.…”

The Ca2+ permeation mechanism of the ryanodine receptor revealed by a multi-site ion model

“…To study the detailed interactions between ions and proteins, we can often use molecular dynamics (MD) simulations to provide microscopic and quantitative insights, thereby obtaining the specific functional mechanisms of the relevant proteins [3][4][5][6] . However, the conventional models of Ca 2+ are far from accurate in calculating the interaction energies between Ca 2+ and proteins [7][8][9] , therefore inadequate to study the precise Ca 2+ -protein interactions.…”