Relationship Between Redox Regulation and β-Adrenergic Responses in the Heart

Abstract

Catecholamines have physiologically important effects on the performance of the heart through the activation of adrenergic receptors. In general, it is known that sympathetic nervous system activation modulates the signaling pathway that controls excitation-contraction coupling (ECC) in the heart. Coordinated myocyte handling of Ca²⁺ is essential for efficient ECC in the heart. A growing body of knowledge on cardiac β-adrenergic receptor (β-AR) signal transduction demonstrates that the agonist-bound β-AR selectively interacts with the stimulatory G protein (G_s), which activates adenylyl cyclase (AC), catalyzing cAMP formation. Subsequently, activation of cAMP-dependent protein kinase A (PKA) leads to phosphorylation of regulatory proteins involved in cardiac ECC and energy metabolism. Published data have shown that the altered cardiac responses in pathological conditions are closely related to the function of the β-AR system. From the current literature it is clear that the β-AR system and its importance in regulating cardiac function under both physiological and pathophysiological situations has attracted the attention of many investigators. Ca²⁺ functions as a critical second messenger in mediating fast intracellular responses in all tissues through signaling proteins to coordinate cell function with different intracellular mechanisms. In addition, the identification of oxidatively sensitive proteins that modulate intracellular signaling mechanisms and the associated generation of reactive oxygen species (ROS) are critical to understanding how cells respond to oxidative stress. Therefore, any disturbance in the intracellular ionic homeostasis due to the excess ROS, was shown to result in the occurrence of impaired cardiac contractile activity. Since β-ARs and AC are known to participate in the regulation of cardiac function, it is possible that the β-AR-linked signal transduction pathway is also affected by ROS.