Optogenetic stimulation of Drosophila heart rate at different temperatures and Ca²⁺ concentrations

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.

SERCA is critical to control the Bowditch effect in the heart

“…The semi intact preparation immersed in artificial hemolymph was electrically stimulated using a conducting device connected to an electro-stimulator and computer. Neutral pH was essential to complete the sequence of stimulation, in agreement with previous studies 27 . A customized chamber was designed to provide electrical field stimulation.…”

Effects of inhibiting mTOR with rapamycin on behavior, development, neuromuscular physiology, and cardiac function in larval Drosophila

“…We have found the larval heart to be very sensitive to variations in intracellular Ca 2+ dynamics (Desai-Shah et al, 2010; Zhu et al, 2016a) and modulation by biogenic amines (Anyagaligbo et al, 2019; Dasari and Cooper, 2006; Dasari et al, 2007; Majeed et al, 2013; Malloy et al, 2016; Titlow et al, 2013) in previous studies. 5-HT in particular increases the heart rate (Majeed et al, 2014; Zhu et al, 2016b) and has direct action on the heart as the pacemaker region in early third instar heart does not have neuronal innervation (Johnstone and Cooper, 2006).…”

Feasibility of Using Adjunctive Optogenetic Technologies in Cardiomyocyte Phenotyping – from the Single Cell to the Whole Heart

“…Since successful application of optogenetics depends on production of a photocurrent large enough to trigger depolarization, expression levels can be critical determinants of experimental outcome. A number of viral [18,25,29,[36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] and non-viral methods [9,10,25,29,31,32,48,[54][55][56][57][58][59][60][61][62][63] have been successfully applied to the cardiomyocyte. For in vivo cardiac application tissue tropism with adeno-associated virus (AAV) types 1 or 6 might be preferable to type 9 used in vitro [64].…”