Action Potential initiation and backpropagation in Neocortical L5 Pyramidal Neuron (Hu et al. 2009)

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Accession:123897
"...Previous computational studies have yielded conflicting conclusions about the role of Na+ channel density and biophysical properties in action potential initiation as a result of inconsistent estimates of channel density. Our modeling studies integrated the immunostaining and electrophysiological results and showed that the lowest threshold for action potential initiation at the distal AIS was largely determined by the density of low-threshold Nav1.6 channels ... Distinct from the function of Nav1.6 channel, the Nav1.2 channel may control action potential backpropagation because of its high density at the proximal AIS and high threshold. ... In conclusion, distal AIS accumulation of Nav1.6 channels determines the low threshold for action potential initiation; whereas proximal AIS accumulation of Nav1.2 channels sets the threshold for the generation of somatodendritic potentials and ensures action potential backpropagation to the soma and dendrites. Thus, Nav1.6 and Nav1.2 channels serve distinct functions in action potential initiation and backpropagation."
Reference:
1 . Hu W, Tian C, Li T, Yang M, Hou H, Shu Y (2009) Distinct contributions of Na(v)1.6 and Na(v)1.2 in action potential initiation and backpropagation. Nat Neurosci 12:996-1002 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Axon; Channel/Receptor;
Brain Region(s)/Organism:
Cell Type(s): Neocortex U1 L2/6 pyramidal intratelencephalic GLU cell; Neocortex U1 L5B pyramidal pyramidal tract GLU cell;
Channel(s): I K; I M; I K,Ca; I Sodium; I Calcium;
Gap Junctions:
Receptor(s):
Gene(s): Nav1.2 SCN2A; Nav1.6 SCN8A;
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Action Potential Initiation; Ion Channel Kinetics; Axonal Action Potentials;
Implementer(s): Hu, Wenqin [huwenqin at ion.ac.cn]; Hou, Han [hh at ion.ac.cn];
Search NeuronDB for information about:  Neocortex U1 L5B pyramidal pyramidal tract GLU cell; Neocortex U1 L2/6 pyramidal intratelencephalic GLU cell; I K; I M; I K,Ca; I Sodium; I Calcium;
// singlecompartmen--an mimic nucleated patch to test properties of inserted soidum channel
//------------------------------------------------------------------------
strdef neuron_name
neuron_name = "scp"

create    soma 
 
soma {
    nseg = 10
    diam = 10
  	L = 10
   
    //-------------------Hou Han 081003 -------------------------------
    // Notice that the time course of sodium channel depends on some external parameters, 
    //   like:
    //      1. celsius (global temperature, influences the most heavily on the time course as shown below)
    //   since we check it with a singlecompartment model, properties of the cell should also be involved: 
    //      2. cm (membrane capacity, the first term "cm * dV/dt" in HH equation, doesn't act on CHANNEL but on CELL)
    //           Ideally, the term "dV/dt" should equal 0 in the V-clamp case (Hodgkin and Huxley,1952), 
    //           but however, NEURON treats all kinds of CLAMPs by a uniform method of solving the whole 
    //           HH equation without these simplifications, so the term "cm * dV/dt" could have a strong 
    //           effect on the time course of the membrane, as well as of the sodium channel. For example, 
    //           setting cm = 100 results in an obvious distortion of the soma.v(0.5) and soma.gna. 
    //      3. Ra (intracellular resistance, little effect on the time course but a little on the amplitude) 
    //           Ra is crucial in those propagation cases, but here (single section, non-propagation case) it just controls 
    //           the "leakage" of channel current to the nearby cytoplasm. So its influence is limited.   
    //
    //   Paradoxically, in the NEURON environment which was designed for neurons rather than channels, it is 
    //      unavoidable that the properties of the "simglecompartment" which we put the channels in will influence
    //      the properties of the channels which we really care about. So I suggest setting CM = 0 AND RA=INFINITE for the 
    //      exclusivity of the channels' properties which reflects the perfection of the mimic single-channel recording.    
    //
    // ( Fortunately, however, the activation and the inactivation KINETICS are determined only 
    //   by the internal factors all defined in the .mod file. )  
    //-----------------------------------------------------------------
    
    
    //---------------------------Hou Han's ---------------------------------
    celsius=37    // TEMPERATURE is crucial whenever time course is concerned !!
                  //    near Line 129 of na.mod:  " tadj = q10^((celsius - temp)/10)   
                  //                                  mtau = 1/tadj/(a+b)   "
                  //     Greg's tadj = 2.3^((37-23)/10)= 2.3^1.4  
                  //     default tadj = 2.3^((6.5-23)/10) =2.3^(-1.65)  
                  //     difference in mtau = 2.3^3.05 = 12.7 times!!
    
  	Ra=10000000000000000000000   //  see the comments above
  	cm=0                         //  see the comments above
		//-------------------------------------------------------------------
    
    
    //---------------------------Greg's------------------------
    //  celsius=37
    //  Ra=100
    //  cm=0.9
    //---------------------------------------------------------
    
    //----------- former settings of NEURON by default---------
    // celsius=6.5
    // Ra=35.4
    // cm=1
    //---------------------------------------------------------

}


 
insert na16
insert na12
insert na
	 

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