Complex oscillations and waves of calcium in pancreatic acinar cells

Abstract We perform a bifurcation analysis of a model of Ca2+ wave propagation in the basal region of pancreatic acinar cells. The model we consider was first presented in Sneyd et al. [J. Sneyd, K. Tsaneva-Atanasova, J.I.E. Bruce, S.V. Straub, D.R. Giovannucci, D.I. Yule, A model of calcium waves in pancreatic and parotid acinar cells, Biophys. J. 85 (2003) 1392–1405], where a partial bifurcation analysis was given of the model in the absence of diffusion. We obtain more complete information about bifurcations of the diffusionless model via numerical studies, then analyse the spatially extended model by numerical investigation of the travelling wave equations and direct numerical solution of the model equations. We find solitary waves in the model equations arising from homoclinic bifurcations in the travelling wave equations. The solitary waves exist and appear to be stable for a significant interval of the primary bifurcation parameter (i.e., the concentration of inositol trisphosphate) but are eventually replaced by irregular spatio-temporal behaviour. The homoclinic bifurcations are related to a number of complicated mathematical structures in the travelling wave equations, including an anomalous homoclinic-Hopf bifurcation, heteroclinic bifurcations between an equilibrium and a periodic orbit, and homoclinic bifurcations of periodic orbits.

[1]  S. V. Straub,et al.  Calcium wave propagation in pancreatic acinar cells: functional interaction of inositol 1,4,5-trisphosphate receptors, ryanodine receptors, and mitochondria. , 2000 .

[2]  J. Sneyd,et al.  Agonist-dependent Phosphorylation of the Inositol 1,4,5-Trisphosphate Receptor , 1999, The Journal of general physiology.

[3]  James Sneyd,et al.  Traveling waves of calcium in a pancreatic acinar cells: model construction and bifurcation analysis , 2000 .

[4]  O H Petersen,et al.  Ca2+ oscillations in pancreatic acinar cells: spatiotemporal relationships and functional implications. , 1993, Cell calcium.

[5]  E. Stuenkel,et al.  Intercellular calcium waves in rat pancreatic acini: mechanism of transmission. , 1996, The American journal of physiology.

[6]  K. Tsaneva-Atanasova,et al.  A model of calcium waves in pancreatic and parotid acinar cells. , 2003, Biophysical journal.

[7]  P. Hirschberg,et al.  Sbil'nikov-Hopf bifurcation , 1993 .

[8]  James A. Yorke,et al.  Explosions of chaotic sets , 2000 .

[9]  Christopher K. R. T. Jones,et al.  The stability of traveling calcium pulses in a pancreatic acinar cell , 2003 .

[10]  Kenjiro Maginu Geometrical Characteristics Associated with Stability and Bifurcations of Periodic Travelling Waves in Reaction-Diffusion Systems , 1985 .

[11]  L. P. Šil'nikov,et al.  ON THREE-DIMENSIONAL DYNAMICAL SYSTEMS CLOSE TO SYSTEMS WITH A STRUCTURALLY UNSTABLE HOMOCLINIC CURVE. II , 1972 .

[12]  O. Petersen,et al.  Transformation of local Ca2+ spikes to global Ca2+ transients: the combinatorial roles of multiple Ca2+ releasing messengers , 2002, The EMBO journal.

[13]  Thomas F. Fairgrieve,et al.  AUTO 2000 : CONTINUATION AND BIFURCATION SOFTWARE FOR ORDINARY DIFFERENTIAL EQUATIONS (with HomCont) , 1997 .

[14]  P. Thorn Spatial aspects of Ca2+ signalling in pancreatic acinar cells. , 1993, The Journal of experimental biology.

[15]  H. Kasai Pancreatic calcium waves and secretion. , 1995, Ciba Foundation symposium.

[16]  Bo Deng,et al.  Šil’nikov-hopf bifurcations , 1995 .

[17]  M. Sanderson,et al.  Mechanisms of calcium oscillations and waves: a quantitative analysis , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[18]  M. Leite,et al.  Ca2+ waves require sequential activation of inositol trisphosphate receptors and ryanodine receptors in pancreatic acini. , 2002, Gastroenterology.

[19]  James Sneyd,et al.  A dynamic model of the type-2 inositol trisphosphate receptor , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[20]  James Sneyd,et al.  A bifurcation analysis of two coupled calcium oscillators. , 2001, Chaos.

[21]  O. Petersen Local calcium spiking in pancreatic acinar cells. , 2007, Ciba Foundation symposium.

[22]  P. Thorn Spatial domains of Ca2+ signaling in secretory epithelial cells. , 1996, Cell calcium.

[23]  Pierre Gaspard,et al.  Homoclinic orbits and mixed-mode oscillations in far-from-equilibrium systems , 1987 .

[24]  Carlo R. Laing,et al.  Successive homoclinic tangencies to a limit cycle , 1995 .

[25]  G. V. D. Heijden Bifurcation sequences in the interaction of resonances in a model deriving from nonlinear rotordynamics: The zipper , 2000 .

[26]  A. Goldbeter Computational approaches to cellular rhythms , 2002, Nature.

[27]  K. Fogarty,et al.  Mechanisms underlying InsP3‐evoked global Ca2+ signals in mouse pancreatic acinar cells , 2000, The Journal of physiology.

[28]  Michael Rademacher,et al.  Homoclinic Bifurcation from Heteroclinic Cycles with Periodic Orbits and Tracefiring of Pulses , 2004 .

[29]  Colin Sparrow,et al.  T-points: A codimension two heteroclinic bifurcation , 1986 .

[30]  James P. Keener,et al.  Mathematical physiology , 1998 .

[31]  S. Schuster,et al.  Modelling of simple and complex calcium oscillations , 2002 .

[32]  James Sneyd,et al.  Cytosolic Ca2+ and Ca2+‐activated Cl− current dynamics: insights from two functionally distinct mouse exocrine cells , 2002, The Journal of physiology.

[33]  O. Petersen Calcium signal compartmentalization. , 2002, Biological research.

[34]  Colin Sparrow,et al.  Local and global behavior near homoclinic orbits , 1984 .