Optogenetics and Optical Voltage Mapping
Investigation of the impact of resting membrane potential and extracellular K+ concentration on cardiac conduction using optogenetics and optical voltage mapping
Rapid action potential propagation in the heart is essential for proper cardiac function. Slow conduction favors re-entry of electrical propagation and rotor formation, the basic mechanism of life-threatening ventricular arrhythmia. The conduction velocity (CV) of electrical waves in the heart depends on cardiomyocyte-cardiomyocyte coupling via gap junctions and the action potential upstroke velocity which is affected by voltage-dependent Na⁺ current and input resistance. Theoretically, an optimal resting membrane potential (RMP) is required for rapid CV at constant intercellular conductance. However, little is known on the influence of RMP on CV because precise experimental control of RMP in cardiac tissue has not been achieved yet due to pharmacological side effects and inhomogeneities of electrical field stimulation.
This project investigates the effects of RMP on CV in the healthy heart and during dysregulation of K⁺ homeostasis, and will generate important mechanistic insights required for improved prevention and treatment of life-threatening ventricular tachycardia.