title: Identification and modelling of fast and slow Ih current components in vestibular ganglion neurons.
abstract: Previous experimental data indicates the hyperpolarization-activated cation (Ih) current, in the inner ear, consists of two components [different hyperpolarization-activated cyclic nucleotide-gated (HCN) subunits] which are impossible to pharmacologically isolate. To confirm the presence of these two components in vestibular ganglion neurons we have applied a parameter identification algorithm which is able to discriminate the parameters of the two components from experimental data. Using simulated data we have shown that this algorithm is able to identify the parameters of two populations of non-inactivated ionic channels more accurately than a classical method. Moreover, the algorithm was demonstrated to be insensitive to the key parameter variations. We then applied this algorithm to Ih current recordings from mouse vestibular ganglion neurons. The algorithm revealed the presence of a high-voltage-activated slow component and a low-voltage-activated fast component. Finally, the electrophysiological significance of these two Ih components was tested individually in computational vestibular ganglion neuron models (sustained and transient), in the control case and in the presence of cAMP, an intracellular cyclic nucleotide that modulates HCN channel activity. The results suggest that, first, the fast and slow components modulate differently the action potential excitability and the excitatory postsynaptic potentials in both sustained and transient vestibular neurons and, second, the fast and slow components, in the control case, provide different information about characteristics of the stimulation and this information is significantly modified after modulation by cAMP.
authors.affiliation: Computing Science & Mathematics, School of Natural Sciences, University of Stirling, Stirling, FK9 4LA, UK.
authors.forename: Christophe B
authors.initials: CB
authors.lastname: Michel
authors.affiliation: DEMAR Team, INRIA/LIRMM, University of Montpellier, Montpellier Cedex 5, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Azevedo Coste
authors.affiliation: Institut National de la Sante et de la Recherche Medicale, Unite Mixte de Recherche 1051, Institut des Neurosciences de Montpellier, Montpellier, France.|Universite Montpellier 1 & 2, Montpellier, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Desmadryl
authors.affiliation: Institut National de la Sante et de la Recherche Medicale, Unite Mixte de Recherche 1051, Institut des Neurosciences de Montpellier, Montpellier, France.|Universite Montpellier 1 & 2, Montpellier, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Puel
authors.affiliation: Institut National de la Sante et de la Recherche Medicale, Unite Mixte de Recherche 1051, Institut des Neurosciences de Montpellier, Montpellier, France.|Universite Montpellier 1 & 2, Montpellier, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Bourien
authors.affiliation: Computing Science & Mathematics, School of Natural Sciences, University of Stirling, Stirling, FK9 4LA, UK.
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Graham
mesh_terms: D000200:Action Potentials; D000465:Algorithms; D000818:Animals; D003198:Computer Simulation; D005260:Female; D017950:Ganglia, Sensory / Q000502:physiology*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000502:physiology*; D008297:Male; D051379:Mice; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D014725:Vestibular Nerve / Q000502:physiology*
chemical_list: D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
keywords: computational modelling; hyperpolarization-activated cation current; vestibular; voltage clamp