How lipids contribute to ion channel function, a fat perspective on direct and indirect interactions

Membrane lipid composition and remodeling influence the function of ion channels. Polyunsaturated fatty acids (PUFAs) and their derivatives modulate ion channel function; whether this effect occurs directly by binding to the protein or indirectly through alteration of membranes' mechanical properties has been difficult to distinguish. There are a large number of studies addressing the effect of fatty acids; recent structural and functional analyses have identified binding sites and provided further evidence for the role of the plasma membrane in ion channel function. Here, we review cation channels that do not share a common topology or lipid-binding signature sequence, but for which there are recent compelling data that support both direct and indirect modulation by PUFAs or their derivatives.