Anion-conducting channelrhodopsins are ion channels that conduct negatively charged ions (such as chloride) and are directly gated by light. All channelrhodopsins use retinal as light-sensitive pigment, but they differ in their ion selectivity. Anion-conducting channelrhodopsins have been used to silence neurons in order to investigate information processing in the brain: Suppressing dendritic calcium spikes in specific neurons with light reduced the ability of mice to perceive a light touch to a whisker.
The first anion-conducting channelrhodopsins were engineered from the cation-conducting Channelrhodopsin-2 by removing negatively charged amino acids from the channel pore. As the main anion of extracellular fluid is chloride (Cl−), anion-conducting channelrhodopsins are also known as “chloride-conducting channelrhodopsins” (ChloC). Naturally occurring anion-conducting channelrhodopsins were later identified in two species of cryptophyte algae (Guillardia theta, Proteomonas sulcata).
Applications
Anion-conducting channelrhodopsins have been used as optogenetic tools to inhibit neuronal activation. When expressed in nerve cells, anion-conducting channelrhodopsins act as light-gated chloride channels. Their effect on the activity of the neuron is comparable to GABAA receptors, ligand-gated chloride channels found in inhibitory synapses: As the chloride concentration in mature neurons is very low, illumination results in an inward flux of negatively charged ions, clamping the neuron at the chloride reversal potential (- 65 mV). Under these conditions, excitatory synaptic inputs are not able to efficiently depolarize the neuron. Illuminating the dendrite prevents the generation of dendritic calcium spikes while illumination of the entire neuron blocks action potential initiation in response to sensory stimulation. Axon terminals, however, have a higher chloride concentration and are therefore excited by ACRs.