Tripartite interactions of PKA catalytic subunit and C-terminal domains of cardiac Ca²⁺ channel may modulate its β-adrenergic regulation.

ABSTRACT:

Background

The β-adrenergic augmentation of cardiac contraction, by increasing the conductivity of L-type voltage-gated Ca_V1.2 channels, is of great physiological and pathophysiological importance. Stimulation of β-adrenergic receptors (βAR) activates protein kinase A (PKA) through separation of regulatory (PKAR) from catalytic (PKAC) subunits. Free PKAC phosphorylates the inhibitory protein Rad, leading to increased Ca²⁺ influx. In cardiomyocytes, the core subunit of Ca_V1.2, Ca_V1.2α₁, exists in two forms: full-length or truncated (lacking the distal C-terminus (dCT)). Signaling efficiency is believed to emanate from protein interactions within multimolecular complexes, such as anchoring PKA (via PKAR) to Ca_V1.2α

SUBMITTER: Oz S 

PROVIDER: S-EPMC11603854 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature