Visualizing voltage dynamics in zebrafish heart.
The zebrafish heart provides a useful vertebrate cardiovascular model with outstanding advantages, including genetic manipulatability, optical accessibility and rapid development. In addition, an emerging topic in cardiotoxicity assay and drug discovery is its use in phenotype-based chemical screening. Here, we report a technique that allows non-invasive voltage mapping in beating heart using a genetically encoded probe for transmembrane potential. Application of the anti-allergy compound astemizole resulted in aberrant propagation of excitation, which accounted for a lack of ventricular contraction. This optical method will provide new opportunities in broad areas of physiological, developmental and pharmacological cardiovascular research.
Tsutsui
Hidekazu
H
Laboratory of Integrative Physiology, Department of Physiology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. tsutsui@phys2.med.osaka-u.ac.jp
Higashijima
Shin-ichi
S
Miyawaki
Atsushi
A
Okamura
Yasushi
Y
D000200:Action Potentials; D000818:Animals; D030801:Animals, Genetically Modified; D018926:Anti-Allergic Agents / Q000633:toxicity; D016589:Astemizole / Q000633:toxicity; D015374:Biosensing Techniques; D024722:Cardiac Myosins / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D056966:Excitation Contraction Coupling / Q000187:drug effects; D036681:Fluorescence Recovery After Photobleaching; D006339:Heart Rate / Q000187:drug effects; D007700:Kinetics; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008856:Microscopy, Fluorescence; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D018994:Myosin Light Chains / Q000235:genetics; D011401:Promoter Regions, Genetic; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
D018926:Anti-Allergic Agents; C527141:Erg protein, zebrafish; D051638:Ether-A-Go-Go Potassium Channels; D008164:Luminescent Proteins; D018994:Myosin Light Chains; D029961:Zebrafish Proteins; C107184:myosin light chain 2; D016589:Astemizole; D024722:Cardiac Myosins