title: Anion channelrhodopsins for inhibitory cardiac optogenetics.
abstract: Optical control of the heart muscle is a promising strategy for cardiology because it is more specific than traditional electrical stimulation, and allows a higher temporal resolution than pharmacological interventions. Anion channelrhodopsins (ACRs) from cryptophyte algae expressed in cultured neonatal rat ventricular cardiomyocytes produced inhibitory currents at less than one-thousandth of the light intensity required by previously available optogenetic tools, such as the proton pump archaerhodopsin-3 (Arch). Because of their greater photocurrents, ACRs permitted complete inhibition of cardiomyocyte electrical activity under conditions in which Arch was inefficient. Most importantly, ACR expression allowed precisely controlled shortening of the action potential duration by switching on the light during its repolarization phase, which was not possible with previously used optogenetic tools. Optical shortening of cardiac action potentials may benefit pathophysiology research and the development of optogenetic treatments for cardiac disorders such as the long QT syndrome.
authors.affiliation: Center for Membrane Biology, Department of Biochemistry &Molecular Biology, University of Texas Health Science Center at Houston - McGovern Medical School, Houston, Texas, USA.
authors.forename: Elena G
authors.initials: EG
authors.lastname: Govorunova
authors.affiliation: Department of Integrative Biology &Pharmacology, University of Texas Health Science Center at Houston - McGovern Medical School, Houston, Texas, USA.
authors.forename: Shane R
authors.initials: SR
authors.lastname: Cunha
authors.affiliation: Center for Membrane Biology, Department of Biochemistry &Molecular Biology, University of Texas Health Science Center at Houston - McGovern Medical School, Houston, Texas, USA.
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Sineshchekov
authors.affiliation: Center for Membrane Biology, Department of Biochemistry &Molecular Biology, University of Texas Health Science Center at Houston - McGovern Medical School, Houston, Texas, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Spudich
mesh_terms: D000200:Action Potentials; D000818:Animals; D000831:Animals, Newborn; D000838:Anions / Q000378:metabolism*; D019843:Archaeal Proteins / Q000378:metabolism; D002478:Cells, Cultured; D000075402:Channelrhodopsins / Q000378:metabolism*; D055724:Electrophysiological Phenomena; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles / Q000166:cytology; D032383:Myocytes, Cardiac / Q000378:metabolism; D062308:Optogenetics; D051381:Rats; D017494:Proton Pumps
chemical_list: D000838:Anions; D019843:Archaeal Proteins; D000075402:Channelrhodopsins; C055476:archaerhodopsin protein, Archaea; D017494:Proton Pumps