Probing spatiotemporal PKA activity at the ryanodine receptor and SERCA2a nanodomains in cardomyocytes

Abstract

Highlights Design a FRET-based biosensor to monitor PKA dynamics at the RyR2 nanodomains in myocytes Stimulation of β1AR promotes PKA activity at both RyR2 and SERCA2a nanodomains whereas stimulation of β2AR does not Inhibition of PDE3 and PDE4 enhances PKA activity at the baseline and after β2AR stimulation Inhibition of Gi selectively permits β2AR signaling to the RyR2 nanodomains but not SERCA2a nanodomains.

Keywords

• β adrenergic receptor (βAR)
• β-blockers
• Phosphodiesterase (PDE)
• Ryanodine receptor (RyR)
• (sarco)endoplasmic reticulum calcium ATPase 2a (SERCA2a)
• Phospholamban (PLB)