title: Slow Calcium-Depolarization-Calcium waves may initiate fast local depolarization waves in ventricular tissue.
abstract: Intercellular calcium waves in cardiac myocytes are a well-recognized, if incompletely understood, phenomenon. In a variety of preparations, investigators have reported multi-cellular calcium waves or triggered propagated contractions, but the mechanisms of propagation and pathological importance of these events remain unclear. Here, we review existing experimental data and present a computational approach to investigate the mechanisms of multi-cellular calcium wave propagation. Over the past 50 years, the standard modeling paradigm for excitable cardiac tissue has seen increasingly detailed models of the dynamics of individual cells coupled in tissue solely by intercellular and interstitial current flow. Although very successful, this modeling regime has been unable to capture two important phenomena: 1) the slow intercellular calcium waves observed experimentally, and 2) how intercellular calcium events resulting in delayed after depolarizations at the cellular level could overcome a source-sink mismatch to initiate depolarization waves in tissue. In this paper, we introduce a mathematical model with subcellular spatial resolution, in which we allow both inter- and intracellular current flow and calcium diffusion. In simulations of coupled cells employing this model, we observe: a) slow inter-cellular calcium waves propagating at about 0.1 mm/s, b) faster Calcium-Depolarization-Calcium (CDC) waves, traveling at about 1 mm/s, and c) CDC-waves that can set off fast depolarization-waves (50 cm/s) in tissue with varying gap-junction conductivity.
authors: Center for Biomedical Computing, Simula Research Laboratory, Norway.
authors: Aslak
authors: A
authors: Tveito
authors: Glenn Terje
authors: GT
authors: Lines
authors: Andrew G
authors: AG
authors: Edwards
authors: Mary M
authors: MM
authors: Maleckar
authors: Anushka
authors: A
authors: Michailova
authors: Johan
authors: J
authors: Hake
authors: Andrew
authors: A
authors: McCulloch
mesh_terms: D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D055724:Electrophysiological Phenomena; D006352:Heart Ventricles / Q000166:cytology*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008564:Membrane Potentials; D008954:Models, Biological; D013997:Time Factors
chemical_list: D002118:Calcium