This is the readme for the model files associated with the paper: Baranauskas G,Martina M (2006) Sodium Currents Activate without a Hodgkin and Huxley- Type Delay in Central Mammalian Neurons J. Neurosci. 26(2):671-684 Abstract: Hodgkin and Huxley established that sodium currents in the squid giant axons activate after a delay, which is explained by the model of a channel with three identical independent gates that all have to open before the channel can pass current (the HH model). It is assumed that this model can adequately describe the sodium current activation time course in all mammalian central neurons, although there is no experimental evidence to support such a conjecture. We performed high temporal resolution studies of sodium currents gating in three types of central neurons. The results show that, within the tested voltage range from -55 to -35 mV, in all of these neurons, the activation time course of the current could be fit, after a brief delay, with a monoexponential function. The duration of delay from the start of the voltage command to the start of the extrapolated monoexponential fit was much smaller than predicted by the HH model. For example, in prefrontal cortex pyramidal neurons, at -46 mV and 12 degrees C, the observed average delay was 140 micros versus the 740 micros predicted by the two-gate HH model and the 1180 micros predicted by the three-gate HH model. These results can be explained by a model with two closed states and one open state. In this model, the transition between two closed states is approximately five times faster than the transition between the second closed state and the open state. This model captures all major properties of the sodium current activation. In addition, the proposed model reproduces the observed action potential shape more accurately than the traditional HH model. --- The model files were supplied by Gytis Baranauskas <baranauskas@elet.polimi.it> A demo is provided that produces the voltage clamp currents for the 6-state Na channel with the protocol from figure 5C. To run the model: simply auto-launch from ModelDB (after NEURON is installed) or download and expand the archive. Compile the mod files by running nrnivmodl (unix) or mknrndll (mswin), or (mac) drag the na2006 folder onto the mknrndll icon in the NEURON application folder. Start the simulation by double clicking on mosinit.hoc (mswin) or typing "nrngui mosinit.hoc" (unix), or dragging either the mosinit.hoc or the vc_demo.hoc file to the nrngui (mac) icon in the NEURON application folder. Additional notes from Gytis Baranauskas: The A-type current and slow outward potassium current were taken from NEURON ModelDB database, Migliore model based on Sakmann & Korngreen paper, the only modifications were shift by +4 mV of voltage dependence of kslow that made easier selection of the parameters. Included are two additional model files kdersej and nachansej that were used during current clamp simulations. They are based on the published model of Mainen, ZF, J Joerges, et al. (1995) A model of spike initiation in neocortical pyramidal neurons. Neuron 15(6): 1427-39. The remaining data (current densities, current injection parameters, modifications of pyramidal demo model soma size, temperature) were inserted manually in the Demo mode of the NEURON employing the provided GUI, for me it was the easiest way. Note: this version contains temperature dependence in all the channels.