A light-gated potassium channel for sustained neuronal inhibition.
                            
                                blue
                            
                            
                                AsLOV2
                            
                            
                                
                                    Cos-7
                                
                            
                                
                                    HEK293T
                                
                            
                                
                                    rat hippocampal neurons
                                
                            
                                
                                    rat in vivo
                                
                            
                                
                                    zebrafish in vivo
                                
                            
                            
                                Neuronal activity control
                            
                            
                            
                            
                            
                        
                        
                        
                        
                            Abstract:
                            Currently available inhibitory optogenetic tools provide short and transient silencing of neurons, but they cannot provide long-lasting inhibition because of the requirement for high light intensities. Here we present an optimized blue-light-sensitive synthetic potassium channel, BLINK2, which showed good expression in neurons in three species. The channel is activated by illumination with low doses of blue light, and in our experiments it remained active over (tens of) minutes in the dark after the illumination was stopped. This activation caused long periods of inhibition of neuronal firing in ex vivo recordings of mouse neurons and impaired motor neuron response in zebrafish in vivo. As a proof-of-concept application, we demonstrated that in a freely moving rat model of neuropathic pain, the activation of a small number of BLINK2 channels caused a long-lasting (>30 min) reduction in pain sensation.