دورية أكاديمية
Pharmacological characterisation of ligand- and voltage-gated ion channels expressed in human iPSC-derived forebrain neurons.
العنوان: | Pharmacological characterisation of ligand- and voltage-gated ion channels expressed in human iPSC-derived forebrain neurons. |
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المؤلفون: | Dage JL; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, 46285, USA., Colvin EM, Fouillet A, Langron E, Roell WC, Li J, Mathur SX, Mogg AJ, Schmitt MG, Felder CC, Merchant KM, Isaac J, Broad LM, Sher E, Ursu D |
المصدر: | Psychopharmacology [Psychopharmacology (Berl)] 2014 Mar; Vol. 231 (6), pp. 1105-24. Date of Electronic Publication: 2014 Jan 16. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 7608025 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-2072 (Electronic) Linking ISSN: 00333158 NLM ISO Abbreviation: Psychopharmacology (Berl) Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Berlin, New York, Springer-Verlag. |
مواضيع طبية MeSH: | Induced Pluripotent Stem Cells/*physiology , Ion Channels/*metabolism , Neurons/*physiology , Prosencephalon/*physiology, Calcium/metabolism ; Calcium Channels/metabolism ; Gene Expression ; Humans ; Induced Pluripotent Stem Cells/drug effects ; Membrane Potentials/drug effects ; Membrane Potentials/physiology ; Neurons/drug effects ; Prosencephalon/drug effects ; RNA, Messenger/metabolism ; Receptors, GABA/metabolism ; Receptors, GABA-A/metabolism ; Receptors, Ionotropic Glutamate/agonists ; Receptors, Ionotropic Glutamate/metabolism ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors ; Receptors, N-Methyl-D-Aspartate/metabolism ; Time Factors ; Voltage-Gated Sodium Channels/metabolism |
مستخلص: | Introduction: Genetic causes, or predisposition, are increasingly accepted to be part of the ethiopathogenesis of many neuropsychiatric diseases. While genes can be studied in any type of cells, their physiological function in human brain cells is difficult to evaluate, particularly in living subjects. Methods: As a first step towards the characterisation of human inducible pluripotent stem cell (iPSC)-derived neurons from autism spectrum disorder (ASD) patients, we used gene expression and functional studies to define the regional identity of the typical forebrain differentiation, demonstrate expression patterns of genes of interest in ASD and understand the properties of 'control' iPSC-derived neurons (iCell-Neurons™), with a focus on receptors and ion channels that play a central role in synaptic physio-pathology. Results and Discussion: The gene expression profile of the iCell-Neurons™ closely resembled that observed in neonatal prefrontal cortex tissues. Functional studies, performed mainly using calcium flux assays, demonstrated the presence of ionotropic glutamate (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate) and gamma-aminobutyric acid type A receptors. Voltage-gated sodium and calcium channels were also identified using similar techniques. Conclusions: Overall, the results reported here suggest that iCell-Neurons™ are a good cellular model of a relatively immature forebrain human neuron population that can be used both as a control in comparison to patients cells, and as host cells in which mutations, insertions and deletions can be used in order to study the molecular mechanisms of ASD and other neurological disorders in an isogenic cellular background. |
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المشرفين على المادة: | 0 (Calcium Channels) 0 (Ion Channels) 0 (RNA, Messenger) 0 (Receptors, GABA) 0 (Receptors, GABA-A) 0 (Receptors, Ionotropic Glutamate) 0 (Receptors, N-Methyl-D-Aspartate) 0 (Voltage-Gated Sodium Channels) SY7Q814VUP (Calcium) |
تواريخ الأحداث: | Date Created: 20140117 Date Completed: 20141112 Latest Revision: 20220309 |
رمز التحديث: | 20240628 |
DOI: | 10.1007/s00213-013-3384-2 |
PMID: | 24429870 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1432-2072 |
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DOI: | 10.1007/s00213-013-3384-2 |