Detecting organelle-specific activity of potassium channels with a DNA nanodevice

Cell surface potassium ion (K⁺) channels regulate nutrient transport, cell migration and intercellular communication by controlling K⁺ permeability and are thought to be active only at the plasma membrane. Although these channels transit the trans-Golgi network, early and recycling endosomes, whether they are active in these organelles is unknown. Here we describe a pH-correctable, ratiometric reporter for K⁺ called pHlicKer, use it to probe the compartment-specific activity of a prototypical voltage-gated K⁺ channel, Kv11.1, and show that this cell surface channel is active in organelles. Lumenal K⁺ in organelles increased in cells expressing wild-type Kv11.1 channels but not after treatment with current blockers. Mutant Kv11.1 channels, with impaired transport function, failed to increase K⁺ levels in recycling endosomes, an effect rescued by pharmacological correction. By providing a way to map the organelle-specific activity of K⁺ channels, pHlicKer technology could help identify new organellar K⁺ channels or channel modulators with nuanced functions.