Atrial-specific pathways for control of intracellular signaling and myocyte function

Abstract

Atrial fibrillation (AF) is a cardiac arrhythmia that arises from electrical and contractile dysfunction in the atria. Atrial function is regulated by a variety of intracellular signaling networks that facilitate rapid communication and coordinate responses of atrial myocytes. In this issue of the JCI, Brandenburg and colleagues describe the identification and characterization of "super-hub" signaling nodes located on atrial axial tubules that regulate atrial contraction. Together, the results of this study provide important insight into the regulation of atrial contraction and describe potential therapeutic targets to be explored in future studies.

Figure 1. Cardiac atrial signaling “hubs” regulate local calcium signaling.

(A) Schematic of the atrial myocyte TT and AT networks and the SR. In this issue, Brandenburg et al. have described an atrial “super hub” (inset), which harbors a unique signaling platform with CRUs and regulatory proteins. RyR2 clusters are differentially regulated at TT and AT domains, potentially due to a distinct constituency of regulatory macromolecular complexes. (B) Schematic showing the distribution of hyperphosphorylated (red) and unphosphorylated (blue) CRUs in association with ATs and TTs at baseline, following β-AR stimulation, and in atrial hypertrophy.