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10.1371/journal.pcbi.1005737 http://scihub22266oqcxt.onion/10.1371/journal.pcbi.1005737 C5599066!5599066 !28863150     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28863150 &cmd=llinks): Failed to open stream: HTTP request failed! 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A single Markov-type kinetic model accounting for the macroscopic currents of all human voltage-gated sodium channel isoforms |pdf=|usr=}}{{28863150 }} gab.com Text A single Markov-type kinetic model accounting for the macroscopic currents of all human voltage-gated sodium channel isoforms JO: PLoS Comput Biol http://www.kidney.de/pget.php?&tw=1&pmid=28863150 #FOAvip Modelling ionic channels represents a fundamental step towards developing biologically detailed neuron models. Until recently, the voltage-gated ion channels have been mainly modelled according to the formalism introduced by the seminal works of Hodgkin and Huxley (HH). However, following the continuing achievements in the biophysical and molecular comprehension of these pore-forming transmembrane proteins, the HH formalism turned out to carry limitations and inconsistencies in reproducing the ion-channels electrophysiological behaviour. At the same time, Markov-type kinetic models have been increasingly proven to successfully replicate both the electrophysiological and biophysical features of different ion channels. However, in order to model even the finest non-conducting molecular conformational change, they are often equipped with a considerable number of states and related transitions, which make them computationally heavy and less suitable for implementation in conductance-based neurons and large networks of those. In this purely modelling study we develop a Markov-type kinetic model for all human voltage-gated sodium channels (VGSCs). The model framework is detailed, unifying (i.e., it accounts for all ion-channel isoforms) and computationally efficient (i.e. with a minimal set of states and transitions). The electrophysiological data to be modelled are gathered from previously published studies on whole-cell patch-clamp experiments in mammalian cell lines heterologously expressing the human VGSC subtypes (from NaV1.1 to NaV1.9). By adopting a minimum sequence of states, and using the same state diagram for all the distinct isoforms, the model ensures the lightest computational load when used in neuron models and neural networks of increasing complexity. The transitions between the states are described by original ordinary differential equations, which represent the rate of the state transitions as a function of voltage (i.e., membrane potential). The kinetic model, developed in the NEURON simulation environment, appears to be the simplest and most parsimonious way for a detailed phenomenological description of the human VGSCs electrophysiological behaviour. Twit Text FOAVip A single Markov-type kinetic model accounting for the macroscopic currents of all human voltage-gated sodium channel isoforms ????PLoS Comput Biol http://www.kidney.de/pget.php?&tw=1&pmid=28863150 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28863150 #FOAvip English Wikipedia <ref>{{Cite pmid|28863150 }}</ref> A single Markov-type kinetic model accounting for the macroscopic currents of all human voltage-gated sodium channel isoforms #MMPMID28863150 Balbi P ; Massobrio P ; Hellgren Kotaleski J PLoS Comput Biol 2017[Sep]; 13 (9 ): e1005737 PMID28863150 show ga Modelling ionic channels represents a fundamental step towards developing biologically detailed neuron models. Until recently, the voltage-gated ion channels have been mainly modelled according to the formalism introduced by the seminal works of Hodgkin and Huxley (HH). However, following the continuing achievements in the biophysical and molecular comprehension of these pore-forming transmembrane proteins, the HH formalism turned out to carry limitations and inconsistencies in reproducing the ion-channels electrophysiological behaviour. At the same time, Markov-type kinetic models have been increasingly proven to successfully replicate both the electrophysiological and biophysical features of different ion channels. However, in order to model even the finest non-conducting molecular conformational change, they are often equipped with a considerable number of states and related transitions, which make them computationally heavy and less suitable for implementation in conductance-based neurons and large networks of those. In this purely modelling study we develop a Markov-type kinetic model for all human voltage-gated sodium channels (VGSCs). The model framework is detailed, unifying (i.e., it accounts for all ion-channel isoforms) and computationally efficient (i.e. with a minimal set of states and transitions). The electrophysiological data to be modelled are gathered from previously published studies on whole-cell patch-clamp experiments in mammalian cell lines heterologously expressing the human VGSC subtypes (from NaV1.1 to NaV1.9). By adopting a minimum sequence of states, and using the same state diagram for all the distinct isoforms, the model ensures the lightest computational load when used in neuron models and neural networks of increasing complexity. The transitions between the states are described by original ordinary differential equations, which represent the rate of the state transitions as a function of voltage (i.e., membrane potential). The kinetic model, developed in the NEURON simulation environment, appears to be the simplest and most parsimonious way for a detailed phenomenological description of the human VGSCs electrophysiological behaviour. |*Models, Neurological [MESH] |Cell Line [MESH] |Computational Biology/*methods [MESH] |Computer Simulation [MESH] |Humans [MESH] |Kinetics [MESH] |Markov Chains [MESH] |Protein Isoforms/chemistry/metabolism/physiology [MESH]A single Markov-type kinetic model accounting for the macroscopic curr(epmc).pdf DeepDyve Pubget Overpricing