AUTHOR=Raimondo Joseph V., Joyce Bradley , Kay Louise , Schlagheck Theresa , Newey Sarah E., Srinivas Shankar , Akerman Colin J. TITLE=A genetically-encoded chloride and pH sensor for dissociating ion dynamics in the nervous system JOURNAL=Frontiers in Cellular Neuroscience VOLUME=7 YEAR=2013 URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2013.00202 DOI=10.3389/fncel.2013.00202 ISSN=1662-5102 ABSTRACT=

Within the nervous system, intracellular Cl− and pH regulate fundamental processes including cell proliferation, metabolism, synaptic transmission, and network excitability. Cl− and pH are often co-regulated, and network activity results in the movement of both Cl− and H+. Tools to accurately measure these ions are crucial for understanding their role under physiological and pathological conditions. Although genetically-encoded Cl− and pH sensors have been described previously, these either lack ion specificity or are unsuitable for neuronal use. Here we present ClopHensorN—a new genetically-encoded ratiometric Cl− and pH sensor that is optimized for the nervous system. We demonstrate the ability of ClopHensorN to dissociate and simultaneously quantify Cl− and H+ concentrations under a variety of conditions. In addition, we establish the sensor's utility by characterizing activity-dependent ion dynamics in hippocampal neurons.