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Synthetic light-activated ion channels for optogenetic activation and inhibition

Please always quote using this URN: urn:nbn:de:bvb:20-opus-177520
  • Optogenetic manipulation of cells or living organisms became widely used in neuroscience following the introduction of the light-gated ion channel channelrhodopsin-2 (ChR2). ChR2 is a non-selective cation channel, ideally suited to depolarize and evoke action potentials in neurons. However, its calcium (Ca2\(^{2+}\)) permeability and single channel conductance are low and for some applications longer-lasting increases in intracellular Ca\(^{2+}\) might be desirable. Moreover, there is need for an efficient light-gated potassium (K\(^{+}\))Optogenetic manipulation of cells or living organisms became widely used in neuroscience following the introduction of the light-gated ion channel channelrhodopsin-2 (ChR2). ChR2 is a non-selective cation channel, ideally suited to depolarize and evoke action potentials in neurons. However, its calcium (Ca2\(^{2+}\)) permeability and single channel conductance are low and for some applications longer-lasting increases in intracellular Ca\(^{2+}\) might be desirable. Moreover, there is need for an efficient light-gated potassium (K\(^{+}\)) channel that can rapidly inhibit spiking in targeted neurons. Considering the importance of Ca\(^{2+}\) and K\(^{+}\) in cell physiology, light-activated Ca\(^{2+}\)-permeant and K\(^{+}\)-specific channels would be welcome additions to the optogenetic toolbox. Here we describe the engineering of novel light-gated Ca\(^{2+}\)-permeant and K\(^{+}\)-specific channels by fusing a bacterial photoactivated adenylyl cyclase to cyclic nucleotide-gated channels with high permeability for Ca\(^{2+}\) or for K\(^{+}\), respectively. Optimized fusion constructs showed strong light-gated conductance in Xenopus laevis oocytes and in rat hippocampal neurons. These constructs could also be used to control the motility of Drosophila melanogaster larvae, when expressed in motoneurons. Illumination led to body contraction when motoneurons expressed the light-sensitive Ca\(^{2+}\)-permeant channel, and to body extension when expressing the light-sensitive K\(^{+}\) channel, both effectively and reversibly paralyzing the larvae. Further optimization of these constructs will be required for application in adult flies since both constructs led to eclosion failure when expressed in motoneurons.show moreshow less

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Metadaten
Author: Sebastian Beck, Jing Yu-Strzelczyk, Dennis Pauls, Oana M. Constantin, Christine E. Gee, Nadine Ehmann, Robert J. Kittel, Georg Nagel, Shiqiang Gao
URN:urn:nbn:de:bvb:20-opus-177520
Document Type:Journal article
Faculties:Medizinische Fakultät / Physiologisches Institut
Fakultät für Biologie / Julius-von-Sachs-Institut für Biowissenschaften
Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Parent Title (English):Frontiers in Neuroscience
Year of Completion:2018
Volume:12
Issue:643
Source:Frontiers in Neuroscience 2018, Volume 12, Article 643. DOI: 10.3389/fnins.2018.00643
DOI:https://doi.org/10.3389/fnins.2018.00643
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Tag:CNG channel; Drosophila melanogaster motoneuron; bPAC; cAMP; calcium; optogenetics; potassium; rat hippocampal neurons
Release Date:2019/04/11
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2018
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International