133 lines
4.1 KiB
Python
133 lines
4.1 KiB
Python
# -*- coding: utf-8 -*-
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"""
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Script to simulate all KCNA1 mutations in STN +Kv1.1 model
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"""
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__author__ = "Nils A. Koch"
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__copyright__ = 'Copyright 2022, Nils A. Koch'
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__license__ = "MIT"
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import numpy as np
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from joblib import Parallel, delayed
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import json
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import os
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from numba import types
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from numba.typed import Dict
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from Code.Functions.Utility_fxns import capacitance, stimulus_init, init_dict
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from Code.Functions.STN_fxns_Kv import STN_Kv_mut
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# model parameters
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dt = 0.01
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sec = 2
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low = 0
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high = 0.005
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number_steps = 100
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initial_period = 1000
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num_gating = 17
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num_current = 9
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d = 61.4
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r = d/2 * 10**-6 # radius in meters
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vol = np.pi * r**3 # volume in liters
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C, surf_area = capacitance(d, 1)
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stim_time, I_in, stim_num, V_m = stimulus_init(low, high, number_steps, initial_period, dt, sec)
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shift, scale, slope_shift, E, currents_included, b_param, g = init_dict(np.array(['m', 'h', 'n', 'a', 'b', 'c', 'd1', 'd2', 'p', 'q', 'r', 's', 'u', 's_mut', 'u_mut','Ca_conc', 'E_Ca']))
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# initialize arrays
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current = np.zeros((num_current, stim_num))
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gating = np.zeros((num_gating, stim_num))
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# initialize dictionary
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ind_dict = Dict.empty(key_type=types.unicode_type, value_type=types.int64, )
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i = 0
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for var in np.array(['m', 'h', 'n', 'q', 'r', 'p', 's', 'u', 's_mut', 'u_mut']):
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ind_dict[var] = i
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i += 1
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i = 0
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for var in np.array(['Na', 'Kd', 'M', 'Kv', 'Kv_mut', 'L', 'Leak']):
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ind_dict[var] = i
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i += 1
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# gating parameters
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b_param['m'] = np.array([-40., -1. , 1.])
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b_param['h'] = np.zeros(4)
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b_param['h'] = np.array([-45.5, 1. , 1., 0.05])
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b_param['n'] = np.array([-41., -1., 1.])
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b_param['p'] = np.array([-56., -1., 1.])
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b_param['q'] = np.array([-85., 1., 1.])
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b_param['r'] = np.array([0.17, -0.08, 1.])
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b_param['a'] = np.array([-45., -14.7, 1.])
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b_param['b'] = np.array([-90., 7.5, 1.])
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b_param['c'] = np.array([-30.6, -5., 1.])
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b_param['d1'] = np.array([-60, 7.5, 1.])
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b_param['d2'] = np.array([0.1, 0.02, 1.])
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b_param['s'] = np.array([-14.16, -10.15, 1.])
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b_param['u'] = np.zeros(4)
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b_param['u'] = np.array([-31., 5.256, 1., 0.245])
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b_param['s_mut'] = np.array([-14.16, -10.15, 1.])
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b_param['u_mut'] = np.zeros(4)
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b_param['u_mut'] = np.array([-31., 5.256, 1., 0.245])
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mut_act_Vhalf_wt = -30.01851851851851
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mut_act_k_wt = -7.7333333333333325
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s_diff_Vhalf = mut_act_Vhalf_wt - b_param['s'][0]
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s_diff_k = mut_act_k_wt - b_param['s'][1]
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b_param['s'][1] = b_param['s'][1] + s_diff_k
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b_param['u'][1] = b_param['u'][1] + s_diff_k
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b_param['s'][0] = b_param['s'][0] + s_diff_Vhalf
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b_param['u'][0] = b_param['u'][0] + s_diff_Vhalf
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b_param['s_mut'][1] = b_param['s_mut'][1] + s_diff_k
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b_param['u_mut'][1] = b_param['u_mut'][1] + s_diff_k
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b_param['s_mut'][0] = b_param['s_mut'][0] + s_diff_Vhalf
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b_param['u_mut'][0] = b_param['u_mut'][0] + s_diff_Vhalf
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# reversal potentials
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E["Na"] = 60.
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E["K"] = -90.
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E["Leak"] = -60.
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# model currents
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currents_included["Na"] = True
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currents_included["Kd"] =True
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currents_included["Kv"] = True
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currents_included["Kv_mut"] = True
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currents_included["L"] = True
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currents_included["T"] = True
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currents_included["Ca_K"] = True
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currents_included["A"] =True
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currents_included["Leak"] = True
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# model conductances
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Kv_ratio = 0.1
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g["Na"] = 49. * surf_area
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g["Kd"] = 27. * (1-Kv_ratio)* surf_area
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if currents_included["Kv_mut"]==True:
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g["Kv"] = 27. * Kv_ratio/2 * surf_area
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else:
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g["Kv"] = 27. * Kv_ratio/2 * surf_area * 2
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g["Kv_mut"] = 27. * Kv_ratio/2 * surf_area
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g["A"] = 5. * surf_area
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g["L"] = 5. * surf_area
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g["T"] = 5. * surf_area
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g["Ca_K"] = 1 * surf_area
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g["Leak"] = 0.035 * surf_area
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V_init = -70
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# save folder
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folder = './KCNA1_mutations/STN_Kv'
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if not os.path.isdir(folder):
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os.makedirs(folder)
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#
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# mutation properties
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mutations = json.load(open("./KCNA1_mutations/mutations_effects_dict.json"))
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prominence = 50
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desired_AUC_width = high/5
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Parallel(n_jobs=8, verbose=9)(
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delayed(STN_Kv_mut)(V_init, g, E, I_in, dt, currents_included, stim_time, stim_num, C, shift, scale, b_param,
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slope_shift, gating, current, prominence, desired_AUC_width, mutations, mut, folder, high, low, number_steps,
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initial_period, sec, vol) for mut in list(mutations.keys()))
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