Making a delay in the activation of an ionic current

NMODL and the Channel Builder.
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finesniper
Posts: 3
Joined: Thu Jan 14, 2016 5:23 am

Making a delay in the activation of an ionic current

Post by finesniper » Thu Jan 14, 2016 12:12 pm

Hello!

I am currently doing a model on reproducing the firing of my recordings from interneurons. The main concenpt of this model is to see, how A-type potassium channels creates a delay in the firing, with the appropriate kinetics. In my recordings, the current does not activate until 1-2 ms after the stimulating square-pulse. Because of this, the A-type currents do not contribute to the repolariztaion, or AHP of the spikes. In the mod file (changing kinetic parameters of Lien 2002), I can not declare a delay, therefore, the tranzient potassium current influences the shape of the spike, which is homogenous in my recordings. I need to freely change the conductance density and kinetics of this current, without affecting the spike parameters.

This is my current mod file

Code: Select all

TITLE KA
: K-A current for hippocampal interneurons from Lien et al (2002)


NEURON {
	SUFFIX ka
	USEION k READ ek WRITE ik
	RANGE  gbar
	GLOBAL minf, hinf, htau, mtau
}

PARAMETER {
	gbar = 0.0002   	(mho/cm2)	
								
	celsius
	ek		(mV)            : must be explicitly def. in hoc
	v 		(mV)
	a0h=0.17
	vhalfh=-105
	q10=3
	hmin=5
}


UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)
	(pS) = (picosiemens)
	(um) = (micron)
} 

ASSIGNED {
	ik 		(mA/cm2)
	minf 		mtau (ms)
	hinf	 	htau (ms)
}
 

STATE { m h}

BREAKPOINT {
        SOLVE states METHOD cnexp
	ik = gbar*m*h*(v - ek)
} 

INITIAL {
	trates(v)
	m=minf  
	h=hinf  
}

DERIVATIVE states {   
        trates(v)      
        m' = (minf-m)/mtau
        h' = (hinf-h)/htau
}

PROCEDURE trates(v) {  
	LOCAL qt
        qt=q10^((celsius-23)/10)
        minf = (1/(1 + exp(-(v+41.4)/26.6)))^4
	mtau=0.5/qt
        hinf = 1/(1 + exp((v+78.5)/6))
	htau = a0h*(v-vhalfh)/qt
	if (htau<hmin/qt) {htau=hmin/qt}
}

Please help me in figuring this out. Thanks!

ted
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Re: Making a delay in the activation of an ionic current

Post by ted » Mon Jan 18, 2016 11:43 am

finesniper wrote:In my recordings, the current does not activate until 1-2 ms after the stimulating square-pulse.
Very strange. Interneurons tend to be small and electrically compact, so this may be difficult to attribute to electrode series resistance or poor space clamp. Has this been reported by others, or is this a unique finding?

If the delay isn't the result of some artifact, are you sure that the current you're seeing isn't caused by calcium-activated potassium channels? That would explain the delay (most calcium entry occurs during repolarization).

A side-comment: this is superficially reminiscent of the Cole-Moore effect, but the delay reported by Cole and Moore happens at the beginning of the response to a depolarizing step.
In the mod file . . . I can not declare a delay
True. NMODL tolerates many crude programming tricks, but that's not one of them. Sounds like you're going to have to come up with a principled explanation of the observation, then express it in a principled mathematical form (kinetic scheme, family of differential equations, or some combination of both), and then express those equations in NMODL.

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