On the dynamical structure of calcium oscillations.
Oscillations in the concentration of free cytosolic Ca2+are an important and ubiquitous control mechanism in many cell types. It is thus correspondingly important to understand the mechanisms that underlie the control of these oscillations and how their period is determined. We show that Class I Ca2+oscillations (i.e., oscillations that can occur at a constant concentration of inositol trisphosphate) have a common dynamical structure, irrespective of the oscillation period. This commonality allows the construction of a simple canonical model that incorporates this underlying dynamical behavior. Predictions from the model are tested, and confirmed, in three different cell types, with oscillation periods ranging over an order of magnitude. The model also predicts that Ca2+oscillation period can be controlled by modulation of the rate of activation by Ca2+of the inositol trisphosphate receptor. Preliminary experimental evidence consistent with this hypothesis is presented. Our canonical model has a structure similar to, but not identical to, the classic FitzHugh-Nagumo model. The characterization of variables by speed of evolution, as either fast or slow variables, changes over the course of a typical oscillation, leading to a model without globally defined fast and slow variables.
Department of Mathematics, University of Auckland, Auckland 1142, New Zealand; sneyd@math.auckland.ac.nz.
James
J
Sneyd
Department of Mathematics, University of Auckland, Auckland 1142, New Zealand.
Jung Min
JM
Han
Department of Pharmacology and Physiology, University of Rochester, Rochester, NY 14642.
Liwei
L
Wang
Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655.
Jun
J
Chen
Department of Mathematics, University of Auckland, Auckland 1142, New Zealand.
Xueshan
X
Yang
Department of Pharmacology, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
Akihiko
A
Tanimura
Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655.
Michael J
MJ
Sanderson
Department of Mathematics, University of Auckland, Auckland 1142, New Zealand.
Vivien
V
Kirk
Department of Pharmacology and Physiology, University of Rochester, Rochester, NY 14642.
David I
DI
Yule
D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003198:Computer Simulation; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D008954:Models, Biological; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism
D053496:Inositol 1,4,5-Trisphosphate Receptors; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D000252:Calcium-Transporting ATPases; D002118:Calcium
cytosolic calcium concentration modeling, multiple time scales; inositol trisphosphate receptor; mathematical modeling