title: TRPM8-Dependent Dynamic Response in a Mathematical Model of Cold Thermoreceptor.
abstract: Cold-sensitive nerve terminals (CSNTs) encode steady temperatures with regular, rhythmic temperature-dependent firing patterns that range from irregular tonic firing to regular bursting (static response). During abrupt temperature changes, CSNTs show a dynamic response, transiently increasing their firing frequency as temperature decreases and silencing when the temperature increases (dynamic response). To date, mathematical models that simulate the static response are based on two depolarizing/repolarizing pairs of membrane ionic conductance (slow and fast kinetics). However, these models fail to reproduce the dynamic response of CSNTs to rapid changes in temperature and notoriously they lack a specific cold-activated conductance such as the TRPM8 channel. We developed a model that includes TRPM8 as a temperature-dependent conductance with a calcium-dependent desensitization. We show by computer simulations that it appropriately reproduces the dynamic response of CSNTs from mouse cornea, while preserving their static response behavior. In this model, the TRPM8 conductance is essential to display a dynamic response. In agreement with experimental results, TRPM8 is also needed for the ongoing activity in the absence of stimulus (i.e. neutral skin temperature). Free parameters of the model were adjusted by an evolutionary optimization algorithm, allowing us to find different solutions. We present a family of possible parameters that reproduce the behavior of CSNTs under different temperature protocols. The detection of temperature gradients is associated to a homeostatic mechanism supported by the calcium-dependent desensitization.
authors.affiliation: Centro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso, Chile.
authors.forename: Erick
authors.initials: E
authors.lastname: Olivares
authors.affiliation: Centro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso, Chile.
authors.forename: Simón
authors.initials: S
authors.lastname: Salgado
authors.affiliation: Centro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso, Chile.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Maidana
authors.affiliation: Centro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso, Chile.
authors.forename: Gaspar
authors.initials: G
authors.lastname: Herrera
authors.affiliation: Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile.
authors.forename: Matías
authors.initials: M
authors.lastname: Campos
authors.affiliation: Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Madrid
authors.affiliation: Centro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso, Chile; Instituto de Neurociencia, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile.
authors.forename: Patricio
authors.initials: P
authors.lastname: Orio
mesh_terms: D000818:Animals; D003080:Cold Temperature; D003198:Computer Simulation; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008962:Models, Theoretical; D009716:Numerical Analysis, Computer-Assisted; D050053:TRPM Cation Channels / Q000378:metabolism*; D013823:Thermoreceptors / Q000378:metabolism*; D013697:Thermosensing / Q000502:physiology*
chemical_list: D050053:TRPM Cation Channels