Mathematical Modeling of Calcium Dynamics in Airway Smooth Muscle Cells
Oscillations in the concentration of free cytoplasmic calcium ([Ca2+] i ) play a vital role in the generation and maintenance of force by airway smooth muscle (ASM) cells. Mathematical models have an important role to play in the study of such complex dynamic phenomena, and can be used to construct and test hypotheses for how such oscillations might occur, and how properties such as the oscillation period might be controlled. We briefly discuss the underlying principles of the construction of mathematical models of calcium dynamics, and show how our current model can be used to understand how oscillations of [Ca2+] i in ASM are the result of a complex interplay between inositol trisphosphate receptors (IP3R) and ryanodine receptors (RyRs). Agonist-stimulated production of inositol trisphosphate (IP3) opens IP3R, resulting in the release of Ca2+ from the endoplasmic reticulum (ER). This released Ca2+ stimulates the release of additional Ca2+ from both IP3R and RyR, leading to cycles of Ca2+ release and reuptake from the ER. In the absence of IP3 (no agonist), when the ER is overloaded with Ca2+ these cycles of release and reuptake are mediated primarily by the RyR. Conversely, in the presence of IP3 (with agonist), when the ER is partially depleted of Ca2+, these cycles are mediated primarily by the IP3R. Thus, an understanding of both IP3R and RyR is required for an understanding of how [Ca2+] i oscillations are controlled in ASM.
KeywordsCalcium oscillations Calcium waves Inositol trisphosphate receptor Ryanodine receptor
This work was supported by National Institutes of Health Grant R01 HL103405 and by the University of Auckland, New Zealand.
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