The effects of chloride flux on drosophila heart rate

Catherine E. Stanley, Alex S. Mauss, Alexander Borst, Robin L. Cooper

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Approaches are sought after to regulate ionotropic and chronotropic properties of the mammalian heart. Electrodes are commonly used for rapidly exciting cardiac tissue and resetting abnormal pacing. With the advent of optogenetics and the use of tissue-specific expression of light-activated channels, cardiac cells cannot only be excited but also inhibited with ion-selective conductance. As a proof of concept for the ability to slow down cardiac pacing, anion-conducting channelrhodopsins (GtACR1/2) and the anion pump halorhodopsin (eNpHR) were expressed in hearts of larval Drosophila and activated by light. Unlike body wall muscles in most animals, the equilibrium potential for Cl is more positive as compared to the resting membrane potential in larval Drosophila. As a consequence, upon activating the two forms of GtACR1 and 2 with low light intensity the heart rate increased, likely due to depolarization and opening of voltage-gated Ca2+ channels. However, with very intense light activation the heart rate ceases, which may be due to Cl shunting to the reversal potential for chloride. Activating eNpHR hyperpolarizes body wall and cardiac muscle in larval Drosophila and rapidly decreases heart rate. The decrease in heart rate is related to light intensity. Intense light activation of eNpHR stops the heart from beating, whereas lower intensities slowed the rate. Even with upregulation of the heart rate with serotonin, the pacing of the heart was slowed with light. Thus, regulation of the heart rate in Drosophila can be accomplished by activating anion-conducting channelrhodopsins using light. These approaches are demonstrated in a genetically amenable insect model.

Original languageEnglish
Article number73
Pages (from-to)1-20
Number of pages20
JournalMethods and Protocols
Issue number3
StatePublished - Sep 2019

Bibliographical note

Funding Information:
This study is part of the NEOMUNE Project, sponsored by the Innovation Fund Denmark (12-132401, to P.S.). Data from Rush University Children's Hospital were provided with support from the National Institutes of Health (NR010009). H-C.L. was supported by the Taiwan China Medical University Hospital (DMR-107-183). J.M. and S.Y. were supported by Sanming Project of Medicine in Shenzhen (SZSM201612045) and Funding for the Construction of Key Medical Disciplines in Shenzhen (Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University). J.v.G. is director of the Dutch Human Milk Bank and a member of the National Health Council. B.C. serves on scientific advisory boards for Nestlé Nutrition Institute and Danone/Nutricia. K.S. is the Director of the Human Milk Bank in Perth Australia and has received support from Medela and Nestlé Nutrition Institute. P.S. has received grant support from ARLA Foods, Medela, Danone/Nutricia, Biofiber-Damino, Mead Johnson Nutrition, and Nestlé Nutrition Institute. F.B. has received travel support for invited lectures from Abbot Nutrition and Nestlé Nutrition Institute and for participation in an expert working group from Danone/Nutricia. N.E. has received speakers' honoraria from Nestlé Nutrition Institute and Danone/Nutricia, and his department has received research support from Prolacta Bioscience and Danone/Nutricia. The other authors declare no conflicts of interest.

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.


  • Chloride channel
  • Drosophila
  • Heart
  • Optogenetics

ASJC Scopus subject areas

  • Biotechnology
  • Structural Biology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)


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