Chasing cardiac physiology and pathology down the caMKII cascade

Alicia Mattiazzi, Rosana A. Bassani, Ariel L. Escobar, Julieta Palomeque, Carlos A. Valverde, Martín Vila Petroff, Donald M Bers

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Calcium dynamics is central in cardiac physiology, as the key event leading to the excitation-contraction coupling (ECC) and relaxation processes. The primary function of Ca<sup>2+</sup> in the heart is the control of mechanical activity developed by the myofibril contractile apparatus. This key role of Ca<sup>2+</sup> signaling explains the subtle and critical control of important events of ECC and relaxation, such as Ca<sup>2+</sup> influx and SR Ca<sup>2+</sup> release and uptake. The multifunctional Ca<sup>2+</sup>-calmodulin-dependent protein kinase II (CaMKII) is a signaling molecule that regulates a diverse array of proteins involved not only in ECC and relaxation but also in cell death, transcriptional activation of hypertrophy, inflammation, and arrhythmias. CaMKII activity is triggered by an increase in intracellular Ca<sup>2+</sup> levels. This activity can be sustained, creating molecular memory after the decline in Ca<sup>2+</sup> concentration, by autophosphorylation of the enzyme, as well as by oxidation, glycosylation, and nitrosylation at different sites of the regulatory domain of the kinase. CaMKII activity is enhanced in several cardiac diseases, altering the signaling pathways by which CaMKII regulates the different fundamental proteins involved in functional and transcriptional cardiac processes. Dysregulation of these pathways constitutes a central mechanism of various cardiac disease phenomena, like apoptosis and necrosis during ischemia/reperfusion injury, digitalis exposure, post-acidosis and heart failure arrhythmias, or cardiac hypertrophy. Here we summarize significant aspects of the molecular physiology of CaMKII and provide a conceptual framework for understanding the role of the CaMKII cascade on Ca<sup>2+</sup> regulation and dysregulation in cardiac health and disease.

Original languageEnglish (US)
Pages (from-to)H1177-H1191
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume308
Issue number10
DOIs
StatePublished - May 15 2015

Fingerprint

Calcium-Calmodulin-Dependent Protein Kinase Type 2
Pathology
Excitation Contraction Coupling
Heart Diseases
Cardiac Arrhythmias
Protein Array Analysis
Digitalis
Myofibrils
Cardiomegaly
Acidosis
Reperfusion Injury
Glycosylation
Hypertrophy
Transcriptional Activation
Cell Death
Necrosis
Phosphotransferases
Heart Failure
Apoptosis
Inflammation

Keywords

  • Arrhythmias
  • Ca<sup>2+</sup>
  • CaMKII
  • Cell death
  • Hypertrophy
  • Ischemia/reperfusion

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Mattiazzi, A., Bassani, R. A., Escobar, A. L., Palomeque, J., Valverde, C. A., Vila Petroff, M., & Bers, D. M. (2015). Chasing cardiac physiology and pathology down the caMKII cascade. American Journal of Physiology - Heart and Circulatory Physiology, 308(10), H1177-H1191. https://doi.org/10.1152/ajpheart.00007.2015

Chasing cardiac physiology and pathology down the caMKII cascade. / Mattiazzi, Alicia; Bassani, Rosana A.; Escobar, Ariel L.; Palomeque, Julieta; Valverde, Carlos A.; Vila Petroff, Martín; Bers, Donald M.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 308, No. 10, 15.05.2015, p. H1177-H1191.

Research output: Contribution to journalArticle

Mattiazzi, A, Bassani, RA, Escobar, AL, Palomeque, J, Valverde, CA, Vila Petroff, M & Bers, DM 2015, 'Chasing cardiac physiology and pathology down the caMKII cascade', American Journal of Physiology - Heart and Circulatory Physiology, vol. 308, no. 10, pp. H1177-H1191. https://doi.org/10.1152/ajpheart.00007.2015
Mattiazzi A, Bassani RA, Escobar AL, Palomeque J, Valverde CA, Vila Petroff M et al. Chasing cardiac physiology and pathology down the caMKII cascade. American Journal of Physiology - Heart and Circulatory Physiology. 2015 May 15;308(10):H1177-H1191. https://doi.org/10.1152/ajpheart.00007.2015
Mattiazzi, Alicia ; Bassani, Rosana A. ; Escobar, Ariel L. ; Palomeque, Julieta ; Valverde, Carlos A. ; Vila Petroff, Martín ; Bers, Donald M. / Chasing cardiac physiology and pathology down the caMKII cascade. In: American Journal of Physiology - Heart and Circulatory Physiology. 2015 ; Vol. 308, No. 10. pp. H1177-H1191.
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