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A Computational Model of Temperature‐Dependent Intracellular pH Regulation
Author(s) -
Contreras Susana,
Quintero Maria,
Putnam Robert,
Santin Joseph,
Hartzler Lynn,
Cordovez Juan
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.860.10
Subject(s) - depolarization , chemistry , biophysics , reversal potential , bicarbonate , intracellular , membrane potential , locus coeruleus , thermodynamics , biochemistry , physics , neuroscience , patch clamp , biology , receptor , organic chemistry , central nervous system
Chemosensitive locus coeruleus neurons from bullfrogs increase their firing rate and reduce chemosensitive responses to CO 2 /H + upon cooling from 20°C to 10°C (Santin et al ., Amer. J. Physiol. Doi:10.1152/ajpregu.00348.2013). To study the observed neuronal response to cold temperature, we developed a computational model of temperature dependent intracellular pH regulation coupled with a single excitable cell model that reproduces the general behavior of a chemosensitive neuron. The model includes a bicarbonate buffering system, a Na + /H + exchanger (NHE), a Na + /K + pump, as well as Na + ,Cl ‐ and K + leak channels. The model is also coupled with a Hodgkin‐Huxley formulation that includes a voltage‐gated Na + channel and a delayed‐rectifying K + (K dr ) channel. The model responses to simulated hypercapnic acidosis are similar to those presented by Boron & De Weer (Boron W.F., and DeWeer. J. Gen. Physiol., 67:91‐12, 1976), producing a slight depolarization of membrane potential together with a drop in intracellular pH. Colder temperature (10°C) decreases the magnitude of the depolarizing response to pH drop in the model, and it also increases the firing rate which is observed upon cooling in locus coeruleus neurons from bullfrogs. Our simulations suggest that these responses are driven mainly by the temperature‐dependence of both Na + /K + pump and the additive effect of the leak ionic fluxes, which could explain the reduced chemosensitive responses to CO 2 /H + upon cooling. Supported by NSF Grant IOS 1257338 (LKH).