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Front Cell Neurosci. 2013 Nov 13;7:202. doi: 10.3389/fncel.2013.00202. eCollection 2013.

A genetically-encoded chloride and pH sensor for dissociating ion dynamics in the nervous system.

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  • 1Department of Pharmacology, University of Oxford Oxford, UK ; UCT/MRC Receptor Biology Unit, Division of Medical Biochemistry, Faculty of Health Sciences, Institute of Infectious Disease and Molecular Medicine, University of Cape Town Cape Town, South Africa.


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.


chloride sensors; fluorescence microscopy; genetic reporters; intracellular chloride; intracellular pH; neural activity; pH sensors

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