Optogenetic Sensors for Monitoring Intracellular Chloride

Here we provide an overview of genetically encoded chloride indicators and their application in imaging intracellular chloride concentration ([Cl−]i). We first compare different chloride sensors and then describe the basic properties of two of these - Clomeleon and SuperClomeleon - in terms of their anion selectivity, pH sensitivity, and binding kinetics. We also describe several approaches that can be used to express Clomeleon in selected populations of neurons. Clomeleon imaging has been used to determine resting [Cl−]i in a variety of neuron types and to determine the shifts in resting [Cl−]i that occur during neuronal development and during pathological conditions. Clomeleon imaging has also been used to monitor dynamic changes in [Cl−]i that are associated with activity of inhibitory synapses. Thus, optogenetic chloride imaging has provided a wide range of novel information about [Cl−]i in neurons and should be generally useful for measuring [Cl−]i within cells.