Since the discovery of the role of Ca2+ in cardiac contractions, it has been clear that many cardiovascular disorders, specifically cardiac arrhythmias are due to irregularities in Ca2+ cycling. We hypothesize that fenoterol, a beta-2 adrenergic receptor agonist, is responsible for inducing abnormal Ca2+ release events that can lead to full cardiac arrhythmias. Ca2+ release events such as sparks, waves, and transients were studied using resonant confocal microscopy in isolated mouse ventricular cardiomyocytes with cumulative concentrations of fenoterol. Fenoterol application in clinically relevant doses can trigger potentially serious cardiac arrhythmias. The data showed that at low fenoterol concentrations, the frequency of Ca2+ sparks and waves were increased and caused Ca2+ oscillations during transients, all of which are indicators of arrhythmogenic Ca2+ activity, via the PKA-mediated pathway. At high concentrations, fenoterol lost its specificity and triggered beta-1AR, activating CaMKII, also resulting in more Ca2+ sparks and wave events and causing oscillations during field-stimulated elicited transients.
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Thesis advisor: Tibbits, Glen
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