Potassium channel-based optogenetic silencing

Nat Commun. 2018 Nov 5;9(1):4611. doi: 10.1038/s41467-018-07038-8.


Optogenetics enables manipulation of biological processes with light at high spatio-temporal resolution to control the behavior of cells, networks, or even whole animals. In contrast to the performance of excitatory rhodopsins, the effectiveness of inhibitory optogenetic tools is still insufficient. Here we report a two-component optical silencer system comprising photoactivated adenylyl cyclases (PACs) and the small cyclic nucleotide-gated potassium channel SthK. Activation of this 'PAC-K' silencer by brief pulses of low-intensity blue light causes robust and reversible silencing of cardiomyocyte excitation and neuronal firing. In vivo expression of PAC-K in mouse and zebrafish neurons is well tolerated, where blue light inhibits neuronal activity and blocks motor responses. In combination with red-light absorbing channelrhodopsins, the distinct action spectra of PACs allow independent bimodal control of neuronal activity. PAC-K represents a reliable optogenetic silencer with intrinsic amplification for sustained potassium-mediated hyperpolarization, conferring high operational light sensitivity to the cells of interest.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / genetics
  • Adenylyl Cyclases / metabolism
  • Adenylyl Cyclases / radiation effects
  • Animals
  • Animals, Genetically Modified
  • Channelrhodopsins / radiation effects
  • Gene Expression / genetics
  • Gene Expression / radiation effects
  • HEK293 Cells
  • Humans
  • Light
  • Mice
  • Models, Animal
  • Myocytes, Cardiac / metabolism
  • Neurons / metabolism
  • Neurons / radiation effects
  • Optogenetics / methods*
  • Potassium Channels / genetics*
  • Potassium Channels / metabolism*
  • Potassium Channels / radiation effects*
  • Rhodopsin / pharmacology
  • Silencer Elements, Transcriptional*
  • Zebrafish


  • Channelrhodopsins
  • Potassium Channels
  • Rhodopsin
  • Adenylyl Cyclases