XPPAUT Differential Equations Tool B.Ermentrout & J.Rinzel Preliminary Remarks • Nonlinear ODEs do not usually have closed form solutions • Numerical solutions are needed • Qualitative analysis: phase plane analysis, bifurcation analysis,stability of steady states • XPPAUT can do all that for us! FOR FREE! Focus of this presentation: We will use XPPAUT for solving : -FitzHugh-Nagumo model of excitable membrane -Population growth model with time delay -Model of intracellular Calcium regulation Fitzhugh-Nagumo Neuron[2 & 3.p161-163 & 4.p422-431] • Simple model of an excitable membrane: dV B.V .(V ).( V ) C.w I applied dt dw (V .w) dt V Membrane potential w Gating variable I applied Current injected into the cell Iapplied=0 Iapplied=0.5 Bifurcation Diagram: Population Growth Model[3.p2-9] • Simple model of growth: dN • dt rN (1 N / k ) r Rate constant of growth k Environmen tal capacity Solution: rt N (0)k .e N (t ) rt [k N (0).(e 1)] N (t ) K as t Sample Curve: Introduction of Time Delay • No closed-form solution available • Dynamic is more interesting dN rN (1 N (t T ) / k ) dt T Time delay for propagatio n of inhibitory signal. Oscillatory Behavior in Model with Delay Calcium Regulation Proc.Natl.Acad.Sci. U.S.A. (1990) 78,1461-1465 d [Ca] v0 v1.[ IP3] pump JRyR k 4 [Ca] k5 [Ca]ER dt d [Ca]ER pump JRyR k5 [Ca]ER dt 2 [Ca]2 [Ca]ER [Ca]4 pump v 2 2 , JRyR v3 . 4 2 2 2 K 2 [Ca] K R [Ca]ER K A [Ca]4 v0 Calcium leak into cytosol from extracellu lar space v1 IP3 induced calcium release from ER. pump ATP dependent calcium pump . JRyR Calcium induced Calcium release from ER k 4 Calcium eliminatio n through plasma membrane k5 Calcium leak from ER vesicles into cytosol Role of IP3() • Base parameter values are: v0 1M / s v3 500 M / s v1 7.3M / s K R 2M 0 M K A 0.9M v2 65M / s K 2 1M k4 10s 1 k5 1s 1 [Ca] vs. Time(s) 0 0.5M Bifurcation Diagram Calcium Entry From Extracellular Space v0 1M / s v0 3.2M / s [Ca] in ER Bifurcation Diagram Conclusion • XPPAUT is a powerful tool for: • Solving ordinary and delay differential equations • Understanding the solution through bifurcation analysis. References • [1] Goldbeter,A.,Dupont,G., and Berridge,M.(1990). Proc.Natl.Acad.Sci.U.S.A. 87 1461-1465. • [2] FitzHugh,R.(1961).Biophys J.1,445-466 • [3] Murray J.(1989) .Mathematical Biology,1st edition,Springer-Verlag,New York. • [4] Fall,C, et al,(2002) Computational Cell Biology,1st edition,Springer-Verlag,New York • [5] Bard Ermentrout XPPAUT5.41 Differential equations tool(August,2002) • www.math.pitt.edu/~bard/xpp/xpp.html
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