Version 2002-08-30 Temperature sensitivity changed:(Behavior unchanged at 27 C) Ingemar Jacobson contributed this model with the comment "... Following compilation the model can be launched from the startatrial1.hoc file - you then just need to start the simulation - I suggest with the variable time step ticked. I had some problems with the intracellular Ca2+-dynamics and for = clarity I had to split it into several files - now it works reasonably well also for CVODE. Having defined the model files of the various cardiac currents it is an easy task to convert the atrial model to more or less any other cardiac cell type. Hopefully this will be of some use for cardiac electrophysiogists. ..." and also "... Perhaps some of the model files can serve as templates for neuronal channels- the molecular correlate for the cardiac Ito is Kv4.3, for IKur it is Kv1.5; for IKr - it is HERG, all these being potassium channels you will find in the CNS. ..." Questions about the model should be directed to the original authors. Questions about the computer implementation should be directed to Dr. Jacobson. Questions about the database presentation should be directed to Michael Hines. Following is a slightly expanded copy of the "about" screen that pops up when the model is executed. Running the model via the mosinit.hoc file (executed automatically by the autolaunch process) will generate the heart action potential shown in the ap.gif file. ------------- The Virtual Human Atrial Cell is assembled for NEURON by Ingemar Jacobson AstraZeneca R & D, Mölndal Sweden emailaddress ingemar.jacobson@astrazeneca.com The model is based on the paper by Marc Courtemanche, Rafael J. Ramirez, and Stanley Nattel. Ionic mechanisms underlying human atrial action potential properties insights from a mathematical model Am J Physiol Heart Circ Physiol 1998 275: H301-H321. and conductance values are adjusted to give appropriate current densities. Pumps, exchangers and an additional electroneutral ion accumulation mechanism are sat so that ion concentrations are stable at a pacing rate of 1 Hz. The kinetics of IKur is modified to fit data of Feng et al Am J Physiol 1998 275(Heart Circ Physiol 44):H1717-H1725. The possibility to include a nonspecific cation-current with kinetics similar to IKur is also given in the IKur mechanism For the intracellular Ca dynamics to work the mechanisms Cadynam, ca_jsr, Ca_jsracc and ca_nsracc have to be inserted. For simulation of intracellular Na+-ion and K+-ion changes the mechanisms Na_acc and K_acc have to be inserted. The model is free to use provided acknowledgement is given to the developers of NEURON nseg = 1 L=100 um diam=16 um cm = 2 uF/cm^2 Vi - intracellular volume 13668um^3 SR -sarcoplasmatic reticulum, JSR - junctional SR - SR release compartment Vrel - SR release compartment volume 96.48um^3 cri - calcium ion conc. in JSR icr - calcium release current from JSR krel - Max. release rate for icr 30mse-1 NSR - network SR - SR uptake compartment Vup - SR uptake compartment volume 1109.52um^3 cui - calcium ion conc. in NSR cupmax - Max. Ca2+ conc. in uptake compartment 15mM Iupmax - Max. uptake Ca2+ current (Iup) by NSR 0.005 mM/ms Kup - [Ca2+]i half-saturation constant for Iup 0.00092mM Trpn - Total troponin conc. in myoplasm 0.07mM Kmtrpn - [Ca2+]i half-saturation constant for troponin 0.0005mM Cmdn - Total calmodulin conc. in myoplasma 0.05 mM Kmcmdn - [Ca2+]i half-saturation constant for calmodulin 0.00238mM Csqn - Total calsequesterin conc. in SR release compartment 10mM Kmcsqn - [Ca2+]JSR (cri) half-saturation constant for calsequesterin 0.8mM IpCamax - Max. Ca2+ pump current (IpCa) 0.00055mA/cm2 gCaL - Max ICaL conductance 0.248mS/cm2 gK1 - Max. IK1 conductance 0.1567mS/cm2 gKr - Max. IKr conductance 0.0588mS/cm2 gKs - Max. IKs conductance 0.258mS/cm2 gKur - Max. IKur conductance 0.13195mS/cm2 gnonspec - Max nonspecific Ication conductance 0 mS/cm2 gnabar - Max INa conductance 15.6 mS/cm2 gbNa - Max. Ibackground (Na) conductance 1.34e-3mS/cm2 gbCa - Max. Ibackground (Ca2+)conductance 2.26e-3mS/cm2 gto - Max. Ito conductance 0.33 mS/cm2 Kneutral - electroneutral K+ - accumulation 3e-5mA/cm2 ImaxNax - Max Ca2+/Na+ exchange current (INaCa) 3.5mA/cm2 KnNacx - [Na+]o half-saturation constant for INaCa 87.5 mM KcNacx - [Ca2+]o half-saturation constant for INaCa 1.38 mM Naneutral - electroneutral Na+ - accumulation 3.5e-5 mA/cm2 INaKmax - Max. Na+/K+-pump current (INaK) 0.00219 mA/cm2 Kmnai - [Na+]i half-saturation constant for InaK 10mM Kmko - [K+]o half-saturation constant for InaK 1.5mM Tauct - scaling factor activation Tauinactf - scaling factor fast inactivation Tauinacts - scaling factor slow inactivation