The stochastic Hodgkin-Huxley model is one of the best-known examples of piecewise deterministic Markov processes (PDMPs), in which the electrical potential across a cell membrane, V(t), is coupled with a mesoscopic Markov jump process representing the stochastic opening and closing of ion channels embedded in the membrane. The rates of the channel kinetics, in turn, are voltage-dependent. Due to this interdependence, an accurate and efficient sampling of the time evolution of the hybrid stochastic systems has been challenging. The current exact simulation methods require solving a voltage-dependent hitting time problem for multiple path-dependent intensity functions with random thresholds. This paper proposes a simulation algorithm that approximates an alternative representation of the exact solution by fitting the log-survival function of the inter-jump dwell time, H(t), with a piecewise linear one. The latter uses interpolation points that are chosen according to the time evolution of the H(t), as the numerical solution to the coupled ordinary differential equations of V(t) and H(t). This computational method can be applied to all PDMPs. Pathwise convergence of the approximated sample trajectories to the exact solution is proven, and error estimates are provided. Comparison with a previous algorithm that is based on piecewise constant approximation is also presented.

3.
D. T.
Gillespie
,
J. Phys. Chem.
81
,
2340
(
1977
).
4.
D. T.
Gillespie
,
J. Comput. Phys.
22
,
403
(
1976
).
5.
A. B.
Bortz
,
M. H.
Kalos
, and
J. L.
Lebowitz
,
J. Comput. Phys.
17
,
10
(
1975
).
6.
J. L.
Doob
,
Trans. Am. Math. Soc.
58
,
455
(
1945
).
7.
A.
Kolmogoroff
,
Math. Ann.
104
,
415
(
1931
).
8.
W.
Feller
,
Trans. Am. Math. Soc.
48
,
488
(
1940
).
9.
M. A.
Gibson
and
J.
Bruck
,
J. Phys. Chem. A
104
,
1876
(
2000
).
10.
D. F.
Anderson
,
J. Chem. Phys.
127
,
214107
(
2007
).
11.
D. T.
Gillespie
,
J. Chem. Phys.
115
,
1716
(
2001
).
12.
13.
D. F.
Anderson
,
J. Chem. Phys.
128
,
054103
(
2008
).
14.
T.
Li
,
Multiscale Model. Simul.
6
,
417
(
2007
).
15.
E. L.
Haseltine
and
J. B.
Rawlings
,
J. Chem. Phys.
117
,
6959
(
2002
).
16.
C. V.
Rao
and
A. P.
Arkin
,
J. Chem. Phys.
118
,
4999
(
2003
).
17.
E. L.
Haseltine
and
J. B.
Rawlings
,
J. Chem. Phys.
123
,
164115
(
2005
).
18.
Y.
Cao
,
D. T.
Gillespie
, and
L. R.
Petzold
,
J. Chem. Phys.
126
,
224101
(
2007
).
19.
E. A.
Mastny
,
E. L.
Haseltine
, and
J. B.
Rawlings
,
J. Chem. Phys.
127
,
094106
(
2007
).
20.
R.
Srivastava
,
E. L.
Haseltine
,
E.
Mastny
, and
J. B.
Rawlings
,
J. Chem. Phys.
134
,
154109
(
2011
).
21.
A. L.
Hodgkin
and
A. F.
Huxley
,
J. Physiol.
116
,
449
(
1952
).
22.
E.
Skaugen
and
L.
Walløe
,
Acta Physiol. Scand.
107
,
343
(
1979
).
23.
B.
Hille
 et al.,
Ion Channels of Excitable Membranes, Vol. 507
(
Sinauer
,
Sunderland, MA
,
2001
).
24.
B.
Hille
,
Ionic channels of excitable membranes
(
Sinauer Associates
,
Sunderland, MA
,
1992
), Vol. 268.
25.
O. P.
Hamill
,
A.
Marty
,
E.
Neher
,
B.
Sakmann
, and
F.
Sigworth
,
Pflügers Arch. Eur. J. Physiol.
391
,
85
(
1981
).
26.
J. R.
Clay
and
L. J.
DeFelice
,
Biophys. J.
42
,
151
(
1983
).
27.
C. C.
Chow
and
J. A.
White
,
Biophys. J.
71
,
3013
(
1996
).
28.
H.
Mino
,
J. T.
Rubinstein
, and
J. A.
White
,
Ann. Biomed. Eng.
30
,
578
(
2002
).
29.
J. A.
Morrison
and
J.
McKenna
,
Stochastic Differential Equations
, edited by
J. B.
Keller
and
H. P.
McKean
(
American Mathematical Society
,
Providence, RI
,
1973
), pp.
97
162
.
30.
M. A.
Pinsky
,
Lectures on Random Evolution
(
World Scientific
,
Singapore
,
1991
).
31.
M. H. A.
Davis
,
J. R. Stat. Soc. Ser. B (Methodol.)
46
,
353
(
1984
).
32.
M. H.
Davis
,
Markov Models and Optimization
(
Chapman & Hall/CRC Press
,
New York
,
1993
).
33.
M.
Jacobsen
,
Point Process Theory and Applications
(
Springer
,
New York
,
2006
).
34.
K.
Pakdaman
,
M.
Thieullen
,
G.
Wainrib
 et al.,
Adv. Appl. Probab.
42
,
761
(
2010
).
35.
M. G.
Riedler
,
M.
Thieullen
, and
G.
Wainrib
,
Electron. J. Probab.
17
,
1
(
2012
).
36.
P. C.
Bressloff
and
J. M.
Newby
,
Phys. Biol.
11
,
016006
(
2014
).
37.
P. C.
Bressloff
and
J. M.
Newby
,
Phys. Rev. E
89
,
042701
(
2014
).
38.
S.
Zeiser
,
U.
Franz
,
O.
Wittich
, and
V.
Liebscher
,
IET Syst. Biol.
2
,
113
(
2008
).
39.
M. G.
Riedler
and
G.
Notarangelo
, e-print arXiv:1310.0392 (
2013
).
40.
D. F.
Anderson
,
B.
Ermentrout
, and
P. J.
Thomas
,
J Comput. Neurosci.
38
,
67
(
2015
).
41.

Here we use to indicate the set of all non-negative integers.

42.
43.

More specifically, 𝝎 is a sequence of independent and U[0,1] distributed random number on the canonical probability space ([0,1],B([0,1]),𝖯). Here [0,1] is the set {𝝎=(ω1,,ωk,):everyωk[0,1]}; B([0,1]) is the σ-algebra generated by all sets of form [a1,b1]××[ak,bk]×[0,1]×[0,1]× with [al,bl][0,1] for l=1,,k; P is the probability measure on B([0,1]) such that 𝖯([a1,b1]××[ak,bk]×[0,1]×[0,1]×)=l==1k(blal). Thus the projection function sequence {𝝎ωk} is independent and U[0,1] distributed.

44.

xy denotes the minimum of x and y.

45.
J.
Rice
and
M.
Rosenblatt
,
Sankhyā: The Indian Journal of Statistics
, Series A (
Springer
,
1976
), Vol. 60.
46.
E.
Süli
and
D. F.
Mayers
,
An Introduction to Numerical Analysis
(
Cambridge University Press
,
2003
).
47.
J. S.
Kim
and
F.
Proschan
,
IEEE Trans. Reliab.
40
,
134
(
1991
).
48.
D. E.
Knuth
,
The Art of Computer Programming: Sorting and Searching
(
Pearson Education
,
1998
).
49.
G. G.
Yin
and
C.
Zhu
,
Hybrid Switching Diffusions: Properties and Applications
(
Springer
,
New York
,
2009
).
50.
X.
Mao
and
C.
Yuan
,
Stochastic Differential Equations with Markovian Switching
(
Imperial College Press
,
UK
,
2006
).
51.
M.
Qian
and
F.-X.
Zhang
,
J. Theor. Probab.
24
,
729
(
2011
).
52.
H.
Qian
,
X.-J.
Zhang
, and
M.
Qian
,
Europhys. Lett.
106
,
10002
(
2014
).

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