Figure 3. Examples of ion channel regulation by lipid competition.

In most excitable cells, K⁺ channels are inhibitory and Ca²⁺ and Na⁺ channels are excitatory. (A) Lipids can regulate this excitability by increasing the opening of K⁺ channels (i, open) and decreasing the gating or voltage sensitivity of Ca²⁺ and Na⁺ channels (ii, closed). In general, PIP₂ (red shading) increases permeability (flow of ions) of the plasma membrane, but numerous channels are exceptions. (B) In some instances, endogenous PA (green shading) can compete with PIP₂ to reverse its effects (coordinated dysregulation). (C) In the presence of ethanol, PLD2 produces an unnatural lipid phosphatidylethanol (PEtOH, blue shading) which can competitively displace and reverse the effect of the endogenous lipid ligand (adapted from Chung et al. [45] under a creative commons license (CC BY-NC-ND 4.0)).