Excitation-Contraction-Energy (ECE) Coupling
An electrical stimulation, i.e., action potential initiates cardiac contraction. Intracellular Ca2+-transient couples action potential and cardiac contraction. Cardiac contraction is also coupled to mitochondria that replenish energy (i.e., ATP) and recycle metabolites (ADP and Pi). InvivoSciences analyzes all those parameters to determine drug-induced or genetically driven changes in ECE coupling.
- Drug-induced cardiac safety analysis using 3D micro-heart tissues (NuHeart™)
- Discovery of compounds to improve cardiac physiology
- Drug target analysis
- Lead optimization
- Biomarker discovery and optimization
- Mechanistic study of inherited cardiac diseases
- Genetic-trio analysis for Precision Medicine Development
Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (iPSCs): CMs cultured on microplates (384/96-well format) are the simplest sample but powerful approach to quickly screen a large number of compounds or combinations of various drugs and culture conditions.
NuHeart™-engineered heart tissues: Three dimensional (3D) cultures of cardiac cells derived from human induced pluripotent stem cells (iPSCs) reconstitute spontaneously beating micro heart tissues in 384/96-well plates (MC-384/96™) or 8-well chambers (MC-8™).
Assays: LITA™ (Live in Tissue Analyzer) measures action potential, Ca-transient, and membrane potential using fluorescent dye-reporters that rapidly change their intensities. Ultra-rapid optical detection devices, FDSS/uCell(Hamamatsu) captures changes in those parameters between cardiac beats. Force of contraction, contractility, contraction duration, and frequency are measured using Palpator™ developed by InvivoSciences.
Cardiac Action Potential: Voltage-sensitive dye (FluoVolt, Life Technologies) reports changes in membrane voltage
Ca2+-transient: Calcium-sensitive dye (Fluo 4 AM, Life Technologies) reports changes in intracellular Ca concentration (see application note published with BMG LABTECH)
Cardiac Force of Contraction: Force of contraction of beating human EHTs (electrically paced or unpaced) under the following conditions:
- Isometric steady state
- Varying loading conditions (different strain, i.e. stretch level)
Mitochondrial Membrane Potential: Positively charged TMRE (tetramethylrhodamine, ethyl ester, Sigma) dye that is permeable to plasma membrane accumulates on negatively charged mitochondrial membrane depending on their activity level.