Synchronized release of Ca2+ from the internal Ca2+ store of cardiac myocytes, the sarcoplasmic reticulum, is essential for a normal heart beat. This is obtained through a sophisticated subcellular organization, the dyad. In dyads...
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Descripción del proyecto
Synchronized release of Ca2+ from the internal Ca2+ store of cardiac myocytes, the sarcoplasmic reticulum, is essential for a normal heart beat. This is obtained through a sophisticated subcellular organization, the dyad. In dyads, a cluster of release channels in the sarcoplasmic reticulum, ryanodine receptors or RyRs, face Ca2+ channels in the cell membrane, the dihydropyrydine receptors or DHPRs. DHPRs provide the Ca2+ influx that triggers opening of RyR. Ca2+ release can also propagate between RyR, leading to Ca2+ waves that can initiate arrhythmias. We hypothesize that RyR that are not within dyads have different properties that may facilitate wave-like propagation and arrhythmias. The objectives are (1) to identify and characterize RyR located between dyads in the sarcomeric space in healthy myocytes (2) to establish whether altered organization and properties of RyRs in chronic atrial fibrillation (AF) contribute to the contractile dysfunction and arrhythmia in AF. My stay in the host lab will provide a clinical and translational perspective to my current knowledge enhancing the potential impact of my research. An interdisciplinary approach for imaging of RyR with access to novel microscopic techniques in the Molecular engineering department and tools for image analysis with the Medical Imaging Center and ESAT will enhance my technological expertise.