I have been interested in exploring how the ionic milieu within an organelle facilitates its lumenal biochemistry and thereby, organelle function. To map these lumenal chemistries, my lab developed a DNA-based, fluorescent reporter technology to quantitatively map ions such as H+, Cl– and Ca2+ within organelles. We can now interrogate organelles of cells in culture, in live organisms and in human patient cells. Our most recent reporter for absolute membrane potential ended a previous misconception by showing that many organelles do in fact, have membrane potential. Today I will discuss two new reporters for organellar Na+ and K+: the final pieces needed to build an electrochemical model for organelle membranes. The only existing electrochemical model of a biological membrane is that of the neuronal cell membrane, first developed by Hodgkin and Huxley in 1952. To accomplish this for organelles we will need input from physicists, cell biologists and electrophysiologists.