Turing instability mediated by voltage and calcium diffusion in paced cardiac cells.

ABSTRACT: In cardiac cells, the coupling between the voltage across the cell membrane (V(m)) and the release of calcium (Ca) from intracellular stores is a crucial ingredient of heart function. Under abnormal conditions and/or rapid pacing, both the action potential duration and the peak Ca concentration in the cell can exhibit well known period-doubling oscillations referred to as "alternans," which have been linked to sudden cardiac death. Fast diffusion of V(m) keeps action potential duration alternans spatially synchronized over the approximately 150-mum-length scale of a cell, but slow diffusion of Ca ions allows Ca alternans within a cell to become spatially asynchronous, as observed in some experiments. This finding raises the question: When are Ca alternans spatially in-phase or out-of-phase on subcellular length scales? This question is investigated by using a spatially distributed model of Ca cycling coupled to V(m). Our main finding is the existence of a Turing-type symmetry breaking instability mediated by V(m) and Ca diffusion that causes Ca alternans to become spontaneously out-of-phase at opposite ends of a cardiac cell. Pattern formation is governed by the interplay of short-range activation of Ca alternans, because of a dynamical instability of Ca cycling, and long-range inhibition of Ca alternans by V(m) alternans through Ca-sensitive membrane ionic currents. These results provide a striking example of a Turing instability in a biological context where the morphogens can be clearly identified, as well as a potential link between dynamical instability on subcellular scales and life-threatening cardiac disorders.

SUBMITTER: Shiferaw Y 

PROVIDER: S-EPMC1458631 | biostudies-literature | 2006 Apr

REPOSITORIES: biostudies-literature