Pyramidal neurons with mutated SCN2A gene (Nav1.2) (Ben-Shalom et al 2017)

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Accession:223955
Model of pyramidal neurons that either hyper or hypo excitable due to SCN2A mutations. Mutations are taken from patients with ASD or Epilepsy
Reference:
1 . Ben-Shalom R, Keeshen CM,Berrios KN, An JY, Sanders SJ, Bender KJ (2017) Opposing effects on NaV1.2 function underlie differences between SCN2A variants observed in individuals with autism spectrum disorder or infantile seizures Biological Psychiatry, epub before print
Model Information (Click on a link to find other models with that property)
Model Type:
Brain Region(s)/Organism:
Cell Type(s): Neocortex V1 pyramidal corticothalamic L6 cell;
Channel(s): I Na,t; I Sodium; I K;
Gap Junctions:
Receptor(s):
Gene(s): Nav1.2 SCN2A;
Transmitter(s):
Simulation Environment: NEURON; MATLAB;
Model Concept(s):
Implementer(s): Ben-Shalom, Roy [bens.roy at gmail.com];
Search NeuronDB for information about:  Neocortex V1 pyramidal corticothalamic L6 cell; I Na,t; I K; I Sodium;
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SCN2A_ASD
Excitability
AdultE1211K
readme.txt *
Cad.mod *
CaH.mod *
CaT.mod *
charge.mod *
h.mod *
Kca.mod *
Kv.mod *
Kv1_axonal.mod *
Kv7.mod *
na8st.mod *
na8st1.mod *
nax8st.mod *
28_04_10_num19.hoc *
Cell parameters.hoc *
charge.hoc *
mosinit.hoc *
scn2aExps.hoc
                            
TITLE calculates Na+/K+ charge overlap and excess Na+ influx 

COMMENT
	Hallermann, de Kock, Stuart and Kole, Nature Neuroscience, 2012
	doi:10.1038/nn.3132
ENDCOMMENT


NEURON {
        SUFFIX charge_     : changed "charge" to "charge_" because of conflicts with NEURON's "charge"
	USEION na READ ina
	USEION k READ ik
        RANGE vmax, vmin, tmax, tmin
        RANGE na_ch, na_ch_overl, overl
	RANGE na_ch_before_peak
	RANGE na_ch_after_peak
	RANGE na_ch_excess_ratio
        RANGE peak_reached
        RANGE peak_time
}

PARAMETER {
	tStart (ms)
	tEnd (ms)
	peak_tolerance (mV)
	peak_lowest (mV)
}


ASSIGNED {
        v (millivolt)
        vmin (millivolt)
        tmin (ms)
        vmax (millivolt)
        tmax (ms)
        na_ch (milliamp/cm2)
        na_ch_overl (milliamp/cm2)
        na_ch_overl_tmp (milliamp/cm2)
	overl

	na_ch_excess_ratio
	na_ch_before_peak
	na_ch_after_peak
        peak_reached
        peak_time
	
	ina  (milliamp/cm2)
	ik  (milliamp/cm2)
}


INITIAL {
        vmin = 1e6
        tmin = 0
        vmax = -1e6
	tmax = 0
        peak_reached = 0
        peak_time = 0
	na_ch = 0
	na_ch_before_peak = 0
	na_ch_after_peak = 0
	na_ch_excess_ratio = 0
	na_ch_overl = 0
	overl = 0
:	tStart = 500
:	tEnd = 1000	
:	peak_tolerance = 0.1	(millivolt)
:	peak_lowest = -60	(millivolt)
}


BREAKPOINT {
VERBATIM
      if (t > tStart) {
		if (t < tEnd) {
			if (v < vmin) {
        		        vmin = v;
                		tmin = t;
		        }
		        if (v > vmax) {
        		        vmax = v;
	                	tmax = t;
		        }
 			na_ch = na_ch + ina;
			na_ch_overl_tmp = ina;				
			if (-ik > ina) {
                		na_ch_overl_tmp = -ik;
		        }
			na_ch_overl = na_ch_overl + na_ch_overl_tmp;
			if (na_ch !=  0) {	//na_ch is negative
                		overl = (na_ch - na_ch_overl) / na_ch;
			}
			if ( (v < vmax - peak_tolerance) && (v > peak_lowest) && (peak_reached == 0) ) {
				peak_reached = 1;
				peak_time = t;
			}
			if (peak_reached == 0) {
				na_ch_before_peak = na_ch_before_peak + ina;			
			} else {
				na_ch_after_peak = na_ch_after_peak + ina;
			}
			if (na_ch_before_peak != 0) {
				na_ch_excess_ratio = (na_ch_before_peak + na_ch_after_peak) / na_ch_before_peak;
			}
		}
	}
ENDVERBATIM
}


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