def ideal_subset_mean_life_time(Q, state1, state2):
"""
Calculate mean life time in a specified subset. Add all rates out of subset
to get total rate out. Skip rates within subset.
Parameters
----------
mec : instance of type Mechanism
state1,state2 : int
State numbers (counting origin 1)
Returns
-------
mean : float
Mean life time.
"""
k = Q.shape[0]
p = qml.pinf(Q)
# Total occupancy for subset.
pstot = np.sum(p[state1-1 : state2])
# Total rate out
if pstot == 0:
mean = 0.0
else:
s = 0.0
for i in range(state1-1, state2):
for j in range(k):
if (j < state1-1) or (j > state2 - 1):
s += Q[i, j] * p[i] / pstot
mean = 1 / s
return mean
def Popen(mec, tres, conc=0, eff='c'):
"""
Calculate equilibrium open probability (Popen) and correct for
unresolved blockages in case of presence of fast pore blocker.
Parameters
----------
mec : dcpyps.Mechanism
The mechanism to be analysed.
tres : float
Time resolution (dead time).
conc : float
Concentration.
Returns
-------
Popen : float
Open probability value at a given concentration.
"""
mec.set_eff(eff, conc)
if tres == 0:
p = qml.pinf(mec.QGG)
popen = np.sum(p[:mec.kA]) / np.sum(p)
else:
hmopen, hmshut = scl.exact_mean_open_shut_time(mec, tres)
popen = (hmopen / (hmopen + hmshut))
if mec.fastblock:
popen = popen / (1 + conc / mec.fastKB)
return popen
def shut_times_between_burst_pdf_components(mec):
"""
Calculate time constants and amplitudes for a PDF of gaps between bursts.
Parameters
----------
mec : dcpyps.Mechanism
The mechanism to be analysed.
Returns
-------
eigs : ndarray, shape(k, 1)
Time constants.
w : ndarray, shape(k, 1)
Component amplitudes.
"""
uA = np.ones((mec.kA, 1))
eigsB, AmatB = qml.eigs(-mec.QBB)
eigsF, AmatF = qml.eigs(-mec.QFF)
pA = qml.pinf(mec.Q)[:mec.kA]
end = np.dot(-mec.QAA, endBurst(mec))
start = pA / np.dot(pA, end)
rowB = np.dot(start, mec.QAB)
rowF = np.dot(start, mec.QAF)
colB = np.dot(mec.QBA, uA)
colF = np.dot(mec.QFA, uA)
wB = -np.dot(np.dot(rowB, AmatB), colB)
wF = np.dot(np.dot(rowF, AmatF), colF)
w = np.append(wB, wF)
eigs = np.append(eigsB, eigsF)
return eigs, w
def shut_times_between_burst_mean(mec):
"""
Calculate the mean length of the gap between bursts (Eq. 3.86, CH82).
Parameters
----------
mec : dcpyps.Mechanism
The mechanism to be analysed.
Returns
-------
m : float
The mean shut time between bursts.
"""
pA = qml.pinf(mec.Q)[:mec.kA]
end = np.dot(-mec.QAA, endBurst(mec))
start = pA / np.dot(pA, end)
uA = np.ones((mec.kA, 1))
GAF, GFA = qml.iGs(mec.Q, mec.kA, mec.kF)
invQFF = -nplin.inv(mec.QFF)
invQBB = -nplin.inv(mec.QBB)
GAB, GBA = qml.iGs(mec.Q, mec.kA, mec.kB)
m1 = np.dot(np.dot(mec.QAF, invQFF), GFA)
m2 = np.dot(np.dot(mec.QAB, invQBB), GBA)
m = np.dot(np.dot(start, m1 - m2), uA)[0]
return m
def transition_frequency(Q):
"""
"""
k = Q.shape[0]
pinf = qml.pinf(Q)
f = Q.copy().transpose()
for i in range(k):
f[i] = f[i] * pinf
f[i,i] = 0
return f.transpose()
def calc_jump (mec, reclen, step, cfunc, cargs):
"""
Calculate response to a concentration pulse directly from Q matrix.
Parameters
----------
mec : dcpyps.Mechanism
The mechanism to be analysed.
reclen : float
Trace length.
step : float
Sampling time interval.
cfunc : function
Concentration profile.
cargs : tuple
Arguments for cfunc(t, cargs).
Returns
-------
t : ndarray
Time samples.
c : ndarray
Concentration profile.
P : ndarray
All state occupancies.
Popen : ndarray
Open probability.
"""
t = np.arange(0, reclen, step)
c = cfunc(t, cargs)
mec.set_eff('c', cargs[1])
pi = qml.pinf(mec.Q)
Pt = np.array([pi.copy()])
for i in range(1, t.shape[0]):
mec.set_eff('c', c[i])
eigenvals, A = qml.eigs_sorted(mec.Q)
w = coefficient_calc(mec.k, A, pi)
pi = P_t(step, eigenvals, w)
Pt = np.append(Pt, [pi.copy()], axis=0)
P = Pt.transpose()
Popen = np.sum(P[: mec.kA], axis=0)
return t, c, Popen, P
def weighted_taus(mec, cmax, width, eff='c'):
"""
Calculate weighted on and off time constants for a square concentration
pulse.
Parameters
----------
mec : dcpyps.Mechanism
The mechanism to be analysed.
cmax : float
Pulse concentration.
width : float
Pulse width.
Returns
-------
tau_on_weighted, tau_off_weighted : floats
Weighted time constants.
"""
mec.set_eff(eff, 0)
eigs0, A0 = qml.eigs_sorted(mec.Q)
P0 = qml.pinf(mec.Q)
mec.set_eff(eff, cmax)
eigsInf, Ainf = qml.eigs_sorted(mec.Q)
w_on = coefficient_calc(mec.k, Ainf, P0)
Pt = P_t(width, eigsInf, w_on)
w_off = coefficient_calc(mec.k, A0, Pt)
ampl_on = np.sum(w_on[:, :mec.kA], axis=1)
max_ampl_on = np.max(np.abs(ampl_on))
rel_ampl_on = ampl_on / max_ampl_on
tau_on_weighted = np.sum(-rel_ampl_on[:-1] * (-1 / eigsInf[:-1]))
tau_on = -1 / eigsInf[:-1]
ampl_off = np.sum(w_off[:, :mec.kA], axis=1)
max_ampl_off = np.max(np.abs(ampl_off))
rel_ampl_off = ampl_off / max_ampl_off
tau_off_weighted = np.sum(rel_ampl_off[: -1] * (-1 / eigs0[:-1]))
tau_off = -1 / eigs0[:-1]
return tau_on_weighted, tau_on, tau_off_weighted, tau_off
def solve_jump(mec, reclen, step, cfunc, cargs, abserr=1.0e-8, relerr=1.0e-6):
"""
Calculate response to a concentration pulse by integration.
Parameters
----------
mec : dcpyps.Mechanism
The mechanism to be analysed.
reclen : float
Trace length.
step : float
Sampling time interval.
cfunc : function
Concentration profile.
cargs : tuple
Arguments for cfunc(t, cargs).
rtol, atol : float, optional
Tolerance limits for the error control performed by the scipy.odeint solver.
Returns
-------
t : ndarray
Time samples.
c : ndarray
Concentration profile.
P : ndarray
All state occupancies.
Popen : ndarray
Open probability.
"""
t = np.arange(0, reclen, step)
mec.set_eff('c', cargs[1])
P0 = qml.pinf(mec.Q)
Pt = scpi.odeint(dPdt, P0, t, args=(mec, cfunc, cargs),
atol=abserr,rtol=relerr)
P = Pt.transpose()
Popen = np.sum(P[: mec.kA], axis=0)
c = cfunc(t, cargs)
return t, c, Popen, P
def phiBurst(mec):
"""
Calculate the start probabilities of a burst (Eq. 3.2, CH82).
phiB = (pCinf * (QCB * GBA + QCA)) / (pCinf * (QCB * GBA + QCA) * uA)
Parameters
----------
mec : dcpyps.Mechanism
The mechanism to be analysed.
Returns
-------
phiB : array_like, shape (1, kA)
"""
uA = np.ones((mec.kA, 1))
pC = qml.pinf(mec.Q)[mec.kE:mec.kG]
GAB, GBA = qml.iGs(mec.Q, mec.kA, mec.kB)
nom = np.dot(pC, (np.dot(mec.QCB, GBA) + mec.QCA))
denom = np.dot(nom, uA)
phiB = nom / denom
return phiB
def printout_occupancies(mec, tres):
"""
"""
str = ('\n\n\n*******************************************\n\n' +
'Open\tEquilibrium\tMean life\tMean latency (ms)\n' +
'state\toccupancy\t(ms)\tto next shutting\n' +
'\t\t\tgiven start in this state\n')
pinf = qml.pinf(mec.Q)
for i in range(mec.k):
if i == 0:
mean_life_A = ideal_subset_mean_life_time(mec.Q, 1, mec.kA)
str += ('Subset A ' +
'\t{0:.5g}'.format(np.sum(pinf[:mec.kA])) +
'\t{0:.5g}\n'.format(mean_life_A * 1000))
if i == mec.kA:
mean_life_B = ideal_subset_mean_life_time(mec.Q, mec.kA + 1, mec.kE)
str += ('\nShut\tEquilibrium\tMean life\tMean latency (ms)\n' +
'state\toccupancy\t(ms)\tto next opening\n' +
'\t\t\tgiven start in this state\n' +
'Subset B ' +
'\t{0:.5g}'.format(np.sum(pinf[mec.kA : mec.kE])) +
'\t{0:.5g}\n'.format(mean_life_B * 1000))
if i == mec.kE:
mean_life_C = ideal_subset_mean_life_time(mec.Q, mec.kE + 1, mec.kG)
str += ('\nSubset C ' +
'\t{0:.5g}'.format(np.sum(pinf[mec.kE : mec.kG])) +
'\t{0:.5g}\n'.format(mean_life_C * 1000))
if i == mec.kG:
mean_life_D = ideal_subset_mean_life_time(mec.Q, mec.kG + 1, mec.k)
str += ('\nSubset D ' +
'\t{0:.5g}'.format(np.sum(pinf[mec.kG : mec.k])) +
'\t{0:.5g}\n'.format(mean_life_D * 1000))
mean = ideal_mean_latency_given_start_state(mec, i+1)
str += ('{0:d}'.format(i+1) +
'\t{0:.5g}'.format(pinf[i]) +
'\t{0:.5g}'.format(-1 / mec.Q[i,i] * 1000) +
'\t{0:.5g}\n'.format(mean * 1000))
expQFF = qml.expQt(mec.QFF, tres)
expQAA = qml.expQt(mec.QAA, tres)
GAF, GFA = qml.iGs(mec.Q, mec.kA, mec.kF)
eGAF = qml.eGs(GAF, GFA, mec.kA, mec.kF, expQFF)
eGFA = qml.eGs(GFA, GAF, mec.kF, mec.kA, expQAA)
phiA = qml.phiHJC(eGAF, eGFA, mec.kA)
phiF = qml.phiHJC(eGFA, eGAF, mec.kF)
str += ('\n\nInitial vector for HJC openings phiOp =\n')
for i in range(phiA.shape[0]):
str += ('\t{0:.5g}'.format(phiA[i]))
str += ('\nInitial vector for ideal openings phiOp =\n')
phiAi = qml.phiA(mec)
for i in range(phiA.shape[0]):
str += ('\t{0:.5g}'.format(phiAi[i]))
str += ('\nInitial vector for HJC shuttings phiSh =\n')
for i in range(phiF.shape[0]):
str += ('\t{0:.5g}'.format(phiF[i]))
str += ('\nInitial vector for ideal shuttings phiSh =\n')
phiFi = qml.phiF(mec)
for i in range(phiF.shape[0]):
str += ('\t{0:.5g}'.format(phiFi[i]))
str += '\n'
return str
def printout(mec, cmax, width, eff='c'):
"""
"""
#TODO: on/off binding
#TODO: move some of calculations from here to separate functions
str = ('\n*******************************************\n' +
'CONCENTRATION JUMPS\n')
gamma = 30 # Conductance in pS
Vm = -80e-3 # Transmembrane potential in V.
mec.set_eff(eff, 0)
P0 = qml.pinf(mec.Q)
eigs0, A0 = qml.eigs_sorted(mec.Q)
str += ('\nEquilibrium occupancies before t=0, at concentration = 0.0:\n')
for i in range(mec.k):
str += ('p00({0:d}) = {1:.5g}\n'.format(i+1, P0[i]))
mec.set_eff(eff, cmax)
Pinf = qml.pinf(mec.Q)
eigsInf, Ainf = qml.eigs_sorted(mec.Q)
w_on = coefficient_calc(mec.k, Ainf, P0)
str += ('\nEquilibrium occupancies at maximum concentration = {0:.5g} mM:\n'
.format(cmax * 1000))
for i in range(mec.k):
str += ('pinf({0:d}) = '.format(i+1) + '{0:.5g}\n'.format(Pinf[i]))
Pt = P_t(width, eigsInf, w_on)
str += ('\nOccupancies at the end of {0:.5g} ms pulse:\n'.
format(width * 1000))
for i in range(mec.k):
str += ('pt({0:d}) = '.format(i+1) + '{0:.5g}\n'.format(Pt[i]))
tau_on_weighted, tau_on, tau_off_weighted, tau_off = weighted_taus(mec, cmax, width, eff='c')
str += ('\nON-RELAXATION for ideal step:\n' +
'Time course for current\n' +
'\nComp\tEigen\t\tTau (ms)\n')
for i in range(mec.k-1):
str += ('{0:d}\t'.format(i+1) +
'{0:.5g}\t\t'.format(eigsInf[i]) +
'{0:.5g}\t\n'.format(-1000 / eigsInf[i])) # convert to ms
ampl_on = np.sum(w_on[:, :mec.kA], axis=1)
cur_on = ampl_on * gamma * Vm
max_ampl_on = np.max(np.abs(ampl_on))
rel_ampl_on = ampl_on / max_ampl_on
area_on = -cur_on[:-1] / eigsInf[:-1]
str += ('\nAmpl.(t=0,pA)\tRel.ampl.\t\tArea(pC)\n')
for i in range(mec.k-1):
str += ('{0:.5g}\t\t'.format(cur_on[i]) +
'{0:.5g}\t\t'.format(rel_ampl_on[i]) +
'{0:.5g}\t\n'.format(area_on[i] * 1000))
str += ('\nWeighted On Tau (ms) = {0:.5g}\n'.format(tau_on_weighted * 1000))
str += ('\nTotal current at t=0 (pA) = {0:.5g}\n'.
format(np.sum(cur_on)))
str += ('Total current at equilibrium (pA) = {0:.5g}\n'.
format(cur_on[-1]))
str += ('Total area (pC) = {0:.5g}\n'.
format(np.sum(area_on)))
#TODO: Current at the end of pulse
ct = cur_on[:-1] * np.exp(width * eigsInf[:-1])
str += ('Current at the end of {0:.5g}'.format(width
* 1000) + ' ms pulse = {0:.5g}\n'.format(np.sum(ct) + cur_on[-1]))
# Calculate off- relaxation.
str += ('\nOFF-RELAXATION for ideal step:\n' +
'Time course for current\n' +
'\nComp\tEigen\t\tTau (ms)\n')
for i in range(mec.k-1):
str += ('{0:d}\t'.format(i+1) +
'{0:.5g}\t\t'.format(eigs0[i]) +
'{0:.5g}\t\n'.format(-1000 / eigs0[i]))
w_off = coefficient_calc(mec.k, A0, Pt)
ampl_off = np.sum(w_off[:, :mec.kA], axis=1)
cur_off = ampl_off * gamma * Vm
max_ampl_off = np.max(np.abs(ampl_off))
rel_ampl_off = ampl_off / max_ampl_off
area_off = np.zeros((mec.k-1))
str += ('\nAmpl.(t=0,pA)\tRel.ampl.\t\tArea(pC)\n')
for i in range(mec.k-1):
area_off[i] = -1000 * cur_off[i] / eigs0[i]
str += ('{0:.5g}\t\t'.format(cur_off[i]) +
'{0:.5g}\t\t'.format(rel_ampl_off[i]) +
'{0:.5g}\t\n'.format(area_off[i]))
str += ('\nWeighted Off Tau (ms) = {0:.5g}\n'.format(tau_off_weighted * 1000))
str += ('\nTotal current at t=0 (pA) = {0:.5g}\n'.
format(np.sum(cur_off)))
str += ('Total current at equilibrium (pA) = {0:.5g}\n'.
format(cur_off[-1]))
str += ('Total area (pC) = {0:.5g}\n'.format(np.sum(area_off)))
return str