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Calcium-permeable channelrhodopsins for the photocontrol of calcium signalling
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Journal Article
Calcium-permeable channelrhodopsins for the photocontrol of calcium signalling
2022
Overview
Channelrhodopsins are light-gated ion channels used to control excitability of designated cells in large networks with high spatiotemporal resolution. While ChRs selective for H
+
, Na
+
, K
+
and anions have been discovered or engineered, Ca
2+
-selective ChRs have not been reported to date. Here, we analyse ChRs and mutant derivatives with regard to their Ca
2+
permeability and improve their Ca
2+
affinity by targeted mutagenesis at the central selectivity filter. The engineered channels, termed CapChR1 and CapChR2 for
ca
lcium-
p
ermeable
ch
annel
r
hodopsins, exhibit reduced sodium and proton conductance in connection with strongly improved Ca
2+
permeation at negative voltage and low extracellular Ca
2+
concentrations. In cultured cells and neurons, CapChR2 reliably increases intracellular Ca
2+
concentrations. Moreover, CapChR2 can robustly trigger Ca
2+
signalling in hippocampal neurons. When expressed together with genetically encoded Ca
2+
indicators in
Drosophila melanogaster
mushroom body output neurons, CapChRs mediate light-evoked Ca
2+
entry in brain explants.
To date, no Ca2 + -selective channelrhodopsins have been characterized. In this study, Fernandez Lahore et al. report two calcium-permeable channelrhodopsins (CapChR1 and 2) for the photocontrol of calcium signalling in excitable tissue.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
