From Bench to Biomolecular Simulation: Phospholipid Modulation of Potassium Channels

Potassium (K(+)) ion channels are crucial in numerous cellular processes as they hyperpolarise a cell through K(+) conductance, returning a cell to its resting potential. K(+) channel mutations result in multiple clinical complications such as arrhythmia, neonatal diabetes and migraines. Since 1995, the regulation of K(+) channels by phospholipids has been heavily studied using a range of interdisciplinary methods such as cellular electrophysiology, structural biology and computational modelling. As a result, K(+) channels are model proteins for the analysis of protein-lipid interactions. In this review, we will focus on the roles of lipids in the regulation of K(+) channels, and how atomic-level structures, along with experimental techniques and molecular simulations, have helped guide our understanding of the importance of phospholipid interactions.