In vivo expression of a light-activatable potassium channel using unnatural amino acids

Ji Yong Kang, Daichi Kawaguchi, Irene Coin, Zheng Xiang, Dennis D.M. O'Leary, Paul A. Slesinger, Lei Wang

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


Optical control of protein function provides excellent spatial-temporal resolution for studying proteins insitu. Although light-sensitive exogenous proteins and ligands have been used to manipulate neuronal activity, a method for optical control of neuronal proteins using unnatural amino acids (Uaa) invivo is lacking. Here, we describe the genetic incorporation of a photoreactive Uaa into the pore of an inwardly rectifying potassium channel Kir2.1. The Uaa occluded the pore, rendering the channel nonconducting, and, on brief light illumination, was released to permit outward K+ current. Expression of this photoinducible inwardly rectifying potassium (PIRK) channel in rat hippocampal neurons created a light-activatable PIRK switch for suppressing neuronal firing. We also expanded the genetic code of mammals to express PIRK channels in embryonic mouse neocortex invivo and demonstrated a light-activated PIRK current in cortical neurons. These principles could be generally expanded to other proteins expressed in the brain to enable optical regulation

Original languageEnglish
Pages (from-to)358-370
Number of pages13
Issue number2
StatePublished - 16 Oct 2013


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