Numerical analysis of the effect of T-tubule location on calcium transient in ventricular myocytes

Biomed Mater Eng. 2014;24(1):1299-306. doi: 10.3233/BME-130932.

Abstract

Intracellular calcium (Ca2+) signaling in cardiac myocytes is vital for proper functioning of the heart. Understanding the intracellular Ca2+ dynamics would give an insight into the functions of normal and diseased hearts. In the current study, spatiotemporal Ca2+ dynamics is investigated in ventricular myocytes by considering Ca2+ release and re-uptake via sarcolemma and transverse tubules (T-tubules), Ca2+ diffusion and buffering in the cytosol, and the blockade of Ca2+ activities associated with the sarcoplasmic reticulum. This study is carried out using a three dimensional (3D) geometric model of a branch of T-tubule extracted from the electron microscopy (EM) images of a partial ventricular myocyte. Mathematical modeling is done by using a system of partial differential equations involving Ca2+, buffers, and membrane channels. Numerical simulation results suggest that a lack of T-tubule structure at the vicinity of the cell surface could increase the peak time of Ca2+ concentration in myocytes. The results also show that T-tubules and mobile buffers play an important role in the regulation of Ca2+ transient in ventricular myocytes.

Keywords: Cardiac myocytes; calcium dynamics; finite element method; numerical analysis; reaction-diffusion equations.

Publication types

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

MeSH terms

  • Algorithms
  • Animals
  • Buffers
  • Calcium / metabolism*
  • Calcium Signaling*
  • Computer Simulation
  • Cytosol / metabolism
  • Diffusion
  • Finite Element Analysis
  • Heart Ventricles / cytology
  • Heart Ventricles / pathology*
  • Humans
  • Microscopy, Electron
  • Models, Theoretical
  • Myocytes, Cardiac / cytology*
  • Patch-Clamp Techniques
  • Sarcolemma / pathology
  • Sarcoplasmic Reticulum / metabolism
  • Time Factors

Substances

  • Buffers
  • Calcium