Genetically Encoded Protein Sensors of Membrane Potential
Organic voltage-sensitive dyes offer very high spatial and temporal resolution for imaging neuronal function. Further progress in imaging activity is expected from the emergent development of genetically encoded fluorescent sensors of membrane potential. These fluorescent protein (FP) voltage sensors overcome some drawbacks of organic voltage sensitive dyes such as non-specificity of cell staining and the low accessibility of the dye to some cell types. In a transgenic animal a genetically encoded sensor could in principle be expressed specifically in any cell type and would have the advantage of staining only the cell population determined by the specificity of the promoter used to drive expression. Challenges remain. First, the response time course of many sensors is slow, with time constants of ∼100 ms. This results in a small fractional fluorescence change, ΔF/F, for action potentials and other brief voltage changes. Second, there are no published reports of attempts to express FP-voltage sensors in transgenic animals. Here we critically review the current status of these developments.
KeywordsFluorescent Protein Fluorescence Resonance Energy Transfer Voltage Sensor Plasma Membrane Expression Voltage Sensor Domain
Supported by NIH grants U24NS057631, DC05259, NS050833, and R21MH064214, and an intramural grant from RIKEN BSI.
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