Abstract
Optogenetics is a revolutionary technique that enables noninvasive activation of electrically excitable cells. In mammals, heart rate has traditionally been modulated with pharmacological agents or direct stimulation of cardiac tissue with electrodes. However, implanted wires have been known to cause physical damage and damage from electrical currents. Here, we describe a proof of concept to optically drive cardiac function in a model organism, Drosophila melanogaster. We expressed the light sensitive channelrhodopsin protein ChR2.XXL in larval Drosophila hearts and examined light-induced activation of cardiac tissue. After demonstrating optical stimulation of larval heart rate, the approach was tested at low temperature and low calcium levels to simulate mammalian heart transplant conditions. Optical activation of ChR2.XXL substantially increased heart rate in all conditions. We have developed a system that can be instrumental in characterizing the physiology of optogenetically controlled cardiac function with an intact heart.
Highlights
Pharmacology is the front-line treatment for intervening in cardiac pathologies that impair heart rate
Heart transplants from mammalian donors are kept at low temperature in a low calcium buffer to reduce
To develop an assay system that simulates those conditions we cold conditioned Drosophila larvae to 10°C and analyzed heart function with the tissue bathed in 10°C physiological saline at different calcium concentrations (Fig. 1)
Summary
Pharmacology is the front-line treatment for intervening in cardiac pathologies that impair heart rate. In addition or in combination with drug applications, direct electrical control of the heart through pacemakers is widely practiced. Pacing of human hearts with electrical stimulating pacemakers or implantable cardioverter defibrillators – which are placed on or nearby cardiac tissue – have saved and prolonged many lives. Novel approaches to control cardiac function are possible with gene therapy or a combination of gene therapy and regulated gene expression (Lee et al 1999), there are various results that warrant caution regarding the safety and efficacy of gene therapy (Giacca and Baker 2011; Jessup et al 2011). More research is needed to enhance the tools and approaches to gene therapy in cardiac tissue to make effective, customized treatments a reality
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