Top: Cell membranes consist of a phospholipid bilayer in which the phospholipid ‘tails’ (zigzags) point inwards, while the polar ‘heads’ (purple ovals) form the membrane surface. On both sides of the bilayer there are interface regions that contain positive ions (blue), negative ions (red) and various polar molecules (including water) that have bound to the membrane. Proteins in the membrane, such as the serotonin transporter (SERT; cyan), allow charged molecules to cross it. These proteins also have a charge associated with their surface: in the case of SERT, a negative charge. This allows SERT to attract positively charged ligands such as cocaine (middle panel). Bottom: the binding of a positive ligand to SERT masks its exposed negative charge. The masking changes the potential (red, negative; blue, positive) in the interface region, making it more positive (as can be seen by comparing the areas marked with curly braces). Burtscher et al. show that this change in potential can be detected as a transient current or a long-lasting apparent capacitance change.