Engineering analysis of cardiac electrical activity in response to calmodulin mutations

E. Entcheva, B. A. Alseikhan, A. Ianuzzi, D. T. Yue, L. Tung

Research output: Contribution to journalConference articlepeer-review

Abstract

Calmodulin (CaM) is a ubiquitous protein involved in different aspects of Ca2+ sensing and regulation in cardiac cells. One of its established roles is in the Ca2+-dependent inactivation of L-type voltage-gated Ca2+ channels. This study examined how mutations in CaM affect action potential duration (APD) in rat neonatal ventricular myocytes, organized in confluent monolayers. Analysis was performed on optically obtained transmembrane potentials in monolayers infected with viral constructs of 4 different CaM mutants. The mean values for 50% and 80% APD (APD50 and APD80) for the treated groups were compared to a control group. The results showed statistically significant APD50 and APD80 prolongations for CaM mutations involving the carboxy-terminus. The most dramatic response resulted in over 200% increase in APD. The experimental data were compared to computer modeling data, using the Luo-Rudy cell model to simulate cardiac cells under various conditions, assuming that the major effects concern Ca2+-dependent inactivation of L-type channels. The model results, where the most dramatic prolongation was only 27%, did not match the experimental data quantitatively. This study suggests a more profound and complex role for CaM in APD regulation than previously thought.

Original languageEnglish (US)
Pages (from-to)1352-1353
Number of pages2
JournalAnnual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume2
StatePublished - Dec 1 2002
EventProceedings of the 2002 IEEE Engineering in Medicine and Biology 24th Annual Conference and the 2002 Fall Meeting of the Biomedical Engineering Society (BMES / EMBS) - Houston, TX, United States
Duration: Oct 23 2002Oct 26 2002

Keywords

  • Action potential duration
  • Calmodulin
  • Cardiac cells

ASJC Scopus subject areas

  • Signal Processing
  • Biomedical Engineering
  • Computer Vision and Pattern Recognition
  • Health Informatics

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