Physiological and pathological roles of protein kinase A in the heart

Cardiovasc Res. 2022 Jan 29;118(2):386-398. doi: 10.1093/cvr/cvab008.


Protein kinase A (PKA) is a central regulator of cardiac performance and morphology. Myocardial PKA activation is induced by a variety of hormones, neurotransmitters, and stress signals, most notably catecholamines secreted by the sympathetic nervous system. Catecholamines bind β-adrenergic receptors to stimulate cAMP-dependent PKA activation in cardiomyocytes. Elevated PKA activity enhances Ca2+ cycling and increases cardiac muscle contractility. Dynamic control of PKA is essential for cardiac homeostasis, as dysregulation of PKA signalling is associated with a broad range of heart diseases. Specifically, abnormal PKA activation or inactivation contributes to the pathogenesis of myocardial ischaemia, hypertrophy, heart failure, as well as diabetic, takotsubo, or anthracycline cardiomyopathies. PKA may also determine sex-dependent differences in contractile function and heart disease predisposition. Here, we describe the recent advances regarding the roles of PKA in cardiac physiology and pathology, highlighting previous study limitations and future research directions. Moreover, we discuss the therapeutic strategies and molecular mechanisms associated with cardiac PKA biology. In summary, PKA could serve as a promising drug target for cardioprotection. Depending on disease types and mechanisms, therapeutic intervention may require either inhibition or activation of PKA. Therefore, specific PKA inhibitors or activators may represent valuable drug candidates for the treatment of heart diseases.

Keywords: AKAP; Adenylyl cyclase; Isoproterenol; Norepinephrine; Phosphodiesterase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Enzyme Activation
  • Heart Diseases / drug therapy
  • Heart Diseases / enzymology*
  • Heart Diseases / pathology
  • Heart Diseases / physiopathology
  • Humans
  • Molecular Targeted Therapy
  • Myocardial Contraction*
  • Myocardium / enzymology*
  • Myocardium / pathology
  • Phosphorylation
  • Protein Kinase Inhibitors / therapeutic use
  • Signal Transduction


  • Protein Kinase Inhibitors
  • Cyclic AMP-Dependent Protein Kinases