Contents

📒 Greenstein 2014

Modeling CaMKII-mediated regulation of L-type Ca(2+) channels and ryanodine receptors in the heart1

Sciwheel.

Introduction

  • Cardiac electrophysiology: experimental research coupled with integrative mathematical modeling
  • CaMKII: an important signaling pathway involving EC coupling (ECC)
  • CaMKII modulates LCCs via a Ca2+-dependent positive-feedback regulatory mechanism known as ICaL facilitation
  • In cardiac myocytes, an activated CaMKII molecule can undergo autophosphorylation by neighboring subunits
  • Oxidative CaMKII activation is also identified.
  • Models: https://www.frontiersin.org/files/Articles/83375/fphar-05-00060-HTML/image_m/fphar-05-00060-t001.jpg

https://www.frontiersin.org/files/Articles/83375/fphar-05-00060-HTML/image_m/fphar-05-00060-g001.jpg

Models of oxidative CaMKII activation and regulation

https://www.frontiersin.org/files/Articles/83375/fphar-05-00060-HTML/image_m/fphar-05-00060-g002.jpg

  • Foteinou et al, 2013
  • future studies will focus on establishing quantitative links between cellular ROS and redox balance, CaMKII activity and function, ECC, and whole-cell electrophysiology
  • the ROS regulation module of Gauthier et al. (2013b) enables its use in larger scale heart models designed to simulate and study how mitochondrial ROS and the functional consequences of its accumulation, such as CaMKII oxidation

Conclusion

  • CaMKII as a nexus point linking heart failure and arrhythmias
  • LCC and RyR activation mechanisms may co-exist in heart failure, and it is likely that both play an important role
  • CaMKII modulation of other targets such as PLB, INa (late), and K+ currents

Reference


  1. Greenstein JL, Foteinou PT, Hashambhoy-Ramsay YL, Winslow RL. Modeling CaMKII-mediated regulation of L-type Ca(2+) channels and ryanodine receptors in the heart. Front. Pharmacol. 2014;5:60. doi:10.3389/fphar.2014.00060. PMC3982069 ↩︎