Action potential of mouse urinary bladder smooth muscle (Mahapatra et al 2018)

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Accession:243842
Urinary incontinence is associated with enhanced spontaneous phasic contractions of the detrusor smooth muscle (DSM). Although a complete understanding of the etiology of these spontaneous contractions is not yet established, it is suggested that the spontaneously evoked action potentials (sAPs) in DSM cells initiate and modulate the contractions. In order to further our understanding of the ionic mechanisms underlying sAP generation, we present here a biophysically detailed computational model of a single DSM cell. First, we constructed mathematical models for nine ion channels found in DSM cells based on published experimental data: two voltage-gated Ca2+ ion channels, an hyperpolarization-activated ion channel, two voltage-gated K+ ion channels, three Ca2+-activated K+ ion channels and a non-specific background leak ion channel. Incorporating these channels, our DSM model is capable of reproducing experimentally recorded spike-type sAPs of varying configurations, ranging from sAPs displaying after-hyperpolarizations to sAPs displaying after-depolarizations. Our model, constrained heavily by physiological data, provides a powerful tool to investigate the ionic mechanisms underlying the genesis of DSM electrical activity, which can further shed light on certain aspects of urinary bladder function and dysfunction.
Reference:
1 . Mahapatra C, Brain KL, Manchanda R (2018) A biophysically constrained computational model of the action potential of mouse urinary bladder smooth muscle. PLoS One 13:e0200712 [PubMed]
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Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism:
Cell Type(s):
Channel(s): ATP-senstive potassium current; I Calcium; I h; I K,Ca; I K; I L high threshold; I T low threshold; IK Bkca; IK Skca;
Gap Junctions: Gap junctions;
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Action Potentials; Action Potential Initiation; Calcium dynamics; Ion Channel Kinetics;
Implementer(s):
Search NeuronDB for information about:  I L high threshold; I T low threshold; I K; I h; I K,Ca; I Calcium; ATP-senstive potassium current; IK Bkca; IK Skca;
TITLE Calcium activated Potassium channel (BK)  

: Author: Chitaranjan Mahapatra (chitaranjan@iitb.ac.in)
: Computational Neurophysiology Lab
: Indian Institute of Technology Bombay, India 

: For details refer: 
: Mahapatra C, Brain KL, Manchanda R, A biophysically constrained computational model of the action potential 
: of mouse urinary bladder smooth muscle. PLOS One (2018) 


NEURON{
SUFFIX BKCAm
USEION k READ ek WRITE ik
USEION ca READ cai 
 RANGE  ik, gkbar, kon,kcoff, kooff, c0o0c, c0c1c, o0c0c,o0o1c, o4c4c,c4o4c, cai, a, b, hva , hvi,sla,sli,o
}

UNITS {
	(molar) = (1/liter)
	(mM)	= (millimolar)
	(S)  	= (siemens)
	(mA) 	= (milliamp)
	(mV) 	= (millivolt)
}

PARAMETER{
gkbar = 0.024 (S/cm2)
kon = 40633
kcoff = 11
kooff = 1.1

c0o0c = 0.02162
c0c1c = 4

o0c0c = 318.1084
o0o1c = 4

o4c4c = 0.35
c4o4c = 0.002

hva = 35
hvi = 15.776
sla = 380
sli = 330


cai	= 0.0001(mM)
}

ASSIGNED{

v (mV)
ek 	(mV)
ik	(mA/cm2)
a
b
o
	

c0c1 (/ms)
c1c0 (/ms)
c1c2 (/ms)
c2c1 (/ms)
c2c3 (/ms)
c3c2 (/ms)
c3c4 (/ms)
c4c3 (/ms)

o0o1 (/ms)
o1o0 (/ms)
o1o2 (/ms)
o2o1 (/ms)
o2o3 (/ms)
o3o2 (/ms)
o3o4 (/ms)
o4o3 (/ms)

c0o0 (/ms)
o0c0 (/ms)

c1o1 (/ms)
o1c1 (/ms)

c2o2 (/ms)
o2c2 (/ms)

c3o3 (/ms)
o3c3 (/ms)

c4o4 (/ms)
o4c4 (/ms)

}


STATE {c0 c1 c2 c3 c4 o0 o1 o2 o3 o4 }

BREAKPOINT {SOLVE kin METHOD sparse
o = o0 + o1 + o2 + o3 + o4



ik = gkbar * o * ( v - ek )
}

 INITIAL { 
 
SOLVE kin STEADYSTATE sparse

}

KINETIC kin {

       rates(v)

~ c0<->c1 (c0c1, c1c0)
~ c1<->c2 (c1c2, c2c1)
~ c2<->c3 (c2c3, c3c2)
~ c3<->c4 (c3c4, c4c3)

~ o0<->o1 (o0o1, o1o0)
~ o1<->o2 (o1o2, o2o1)
~ o2<->o3 (o2o3, o3o2)
~ o3<->o4 (o3o4, o4o3)

~ c0<->o0 (c0o0, o0c0)
~ c1<->o1 (c1o1, o1c1)
~ c2<->o2 (c2o2, o2c2)
~ c3<->o3 (c3o3, o3c3)
~ c4<->o4 (c4o4, o4c4)

CONSERVE c0 + c1 + c2 + c3 + c4 + o0 + o1 + o2 + o3 + o4 = 1
}

PROCEDURE rates(v(mV)){
UNITSOFF
a = exp (hva*v/sla)
b = exp (hvi*v/sli)

c0o0 = c0o0c   * a
c1o1 = 0.000869  * a
c2o2 = 0.0000281 * a
c3o3 = 0.000781  * a
c4o4 = c4o4c * a

o0c0 = o0c0c *  b
o1c1 = 144.1736 * b
o2c2 = 32.6594 * b
o3c3 = 0.095312 * b
o4c4 = o4c4c * b
UNITSON
}

PROCEDURE prates(cai(mM)){

UNITSOFF

c0c1 = c0c1c * kon * cai
c1c2 = 3 * kon * cai
c2c3 = 2 * kon * cai
c3c4 = kon * cai

c4c3 = 4 * kcoff * cai
c3c2 = 3 * kcoff * cai
c2c1 = 2 * kcoff * cai
c1c0 =  kcoff * cai

o0o1 = 4 * kon * cai
o1o2 = 3 * kon * cai
o2o3 = 2 * kon * cai
o3o4 =  kon * cai

o4o3 = 4 * kooff * cai
o3o2 = 3 * kooff * cai
o2o1 = 2 * kooff * cai
o1o0 =  kooff * cai

UNITSON
}