Acute Optogenetic Modulation of Cardiac Twitch Dynamics Explored Through Modeling

Area of Science:

• Biophysics
• Cardiovascular Physiology
• Optogenetics

Background:

• Optogenetics allows light-induced control of cellular membrane potentials.
• Application to muscle cells enables "optomechanics," controlling mechanical events with light.

Purpose of the Study:

• To investigate the hypothesis that optomechanical control can modulate the strength and duration of cardiomyocyte contractions.
• To develop and test hybrid light-electrical stimulation protocols for cardiomyocyte control.

Main Methods:

• Constructed an electromechanical model of a human ventricular cardiomyocyte.
• Incorporated a representation of channelrhodopsin-2 (ChR2), a light-activated ion channel.
• Developed two hybrid stimulus protocols combining light and electrical stimuli.

Main Results:

• A subthreshold optical stimulus followed by electrical stimulation resulted in graded inhibition of twitch force and prolonged Ca2+ transient.
• Electrical stimulation followed by a long light pulse prolonged the action potential and Ca2+ transient, altering relaxation rate without changing peak force.

Conclusions:

• Demonstrated the feasibility of acute, optomechanical manipulation of cardiomyocyte contraction.
• Suggests optomechanics can probe cardiac sarcomere dynamics without altering intrinsic properties.
• The developed model allows for the design of novel experimental stimulus protocols.