Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093, USA.
Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):2114-9. doi: 10.1073/pnas.1120694109. Epub 2012 Jan 24.
Fluorescence imaging is an attractive method for monitoring neuronal activity. A key challenge for optically monitoring voltage is development of sensors that can give large and fast responses to changes in transmembrane potential. We now present fluorescent sensors that detect voltage changes in neurons by modulation of photo-induced electron transfer (PeT) from an electron donor through a synthetic molecular wire to a fluorophore. These dyes give bigger responses to voltage than electrochromic dyes, yet have much faster kinetics and much less added capacitance than existing sensors based on hydrophobic anions or voltage-sensitive ion channels. These features enable single-trial detection of synaptic and action potentials in cultured hippocampal neurons and intact leech ganglia. Voltage-dependent PeT should be amenable to much further optimization, but the existing probes are already valuable indicators of neuronal activity.
荧光成像是监测神经元活动的一种有吸引力的方法。光学监测电压的一个关键挑战是开发能够对跨膜电位变化做出大而快速响应的传感器。我们现在提出了通过从电子供体通过合成分子线到荧光团的光诱导电子转移（PeT）的调制来检测神经元中电压变化的荧光传感器。与电致变色染料相比，这些染料对电压的响应更大，但与基于疏水性阴离子或电压敏感离子通道的现有传感器相比，其动力学更快，电容增加更小。这些特性使我们能够在培养的海马神经元和完整的水蛭神经节中单次检测突触和动作电位。电压依赖性 PeT 应该可以进一步优化，但现有的探针已经是神经元活动的有价值的指标。
