Investigating cardiac β-adrenergic nuclear signaling with FRET-based biosensors

Abstract

By activating membrane β-adrenergic receptors (β-AR), noradrenaline and adrenaline are the most powerful stimulators of cardiac function. β-ARs are coupled to the synthesis of cAMP, which activates the cAMP-dependent protein kinase (PKA). PKA regulates the key proteins of excitation-contraction coupling but also gene expression. While an acute activation of the cAMP/PKA pathway allows adaptation of cardiac output to exercise, its chronic activation is deleterious by promoting pathological remodeling of the heart. The use of probes based on fluorescence resonance energy transfer (FRET) and located specifically at the level of the cytoplasm or the nucleus make it possible to highlight the differential mechanisms by which β-ARs control PKA activation in these two compartments. The characterization of these mechanisms is important in order to better understand the deleterious effects of chronic activation of the β-adrenergic pathway in the heart.