Rosas2015 - Caffeine-induced luminal SR calcium changes

This SBML model reproduced the calcium release from SR by application of 20 mM or 2mM caffeine, described in the paper. * Ca_i_Total and Ca_SR_Total respectively represent the total calcium concentration in the sarcoplasm and in the sarcoplasmic reticulum. * Ca_i and Ca_SR respectively represent the free calcium concentration in the sarcoplasm and the sarcoplasmic reticulum. * J1 is the calcium flux due to all mechanisms (except SERCA pumps) that remove the excess of calcium from the sarcoplasm. * J2 is the calcium flux from the reticulum to the sarcoplasm via the ryanodine receptors (RyR) present in the reticulum membrane. * J3 is the calcium flux from the sarcoplasm to the reticulum by the SERCA pumps located in the reticulum membrane. *The parameters are a, b, B c, Ca_i_basal, Ca_SR_basal, caff, csq, gamma, KC, kf, KR, Ks, nf, ns and nv. * The value of KC for the model were calculated for J2=J3, after substituting Ca_i=Ca_i_basal, Ca_SR=Ca_SR_basal and caff=0. * Po represents the RyR open probability based on CICR. * Caffeine (caff)** increases the calcium affinity of smooth muscle's RyR so they open even when calcium is at basal level. ** Due to caffeine-induced calcium release, a 5 seconds pulse of caffeine (20 mM) was applied (event called Caff_ON) at 10 seconds after the simulation starts. The event called Caff_OFF starts when the pulse of caffeine finished (caff=0). * PE denotes the concentration of calcium binding sites. * Xi=Ca_SR_Total+PE+KR *In order to reproduce the dynamics of calcium following the application of 2 mM of caffeine, the value of some parameters needs to be change: b=35, Ca_i_basal=9.257e-6, gamma=7.45, caff=0.002 and the initial condition for Ca_i_Total=9.257e-6. *The unit of the calcium concentration is mol/L. * The unit of time is second. *The original SBML code was exported from COPASI 4.12 (Build 81).