دورية أكاديمية
Alternative Splicing of the TRPC3 Ion Channel Calmodulin/ IP3 Receptor-Binding Domain in the Hindbrain Enhances Cation Flux
| العنوان: | Alternative Splicing of the TRPC3 Ion Channel Calmodulin/ IP3 Receptor-Binding Domain in the Hindbrain Enhances Cation Flux |
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| المؤلفون: | Kim, YS, Wong, AC, Power, J, Tadros, SF, Klugmann, M, Moorhouse, AJ, Bertrand, PP, Housley, GD |
| المصدر: | urn:ISSN:0270-6474 ; urn:ISSN:1529-2401 ; The Journal of Neuroscience, 32, 33, 11414-11423 |
| بيانات النشر: | Society for Neuroscience |
| سنة النشر: | 2012 |
| المجموعة: | UNSW Sydney (The University of New South Wales): UNSWorks |
| مصطلحات موضوعية: | Neurosciences, Rare Diseases, Brain Disorders, Neurological, Alternative Splicing, Amino Acid Sequence, Analysis of Variance, Animals, Biophysical Phenomena, Calcium, Calmodulin, Carbachol, Cell Line, Transformed, Cerebellum, Cholinergic Agonists, Excitatory Amino Acid Agents, Female, Genistein, Guinea Pigs, Humans, Inositol 1,4,5-Trisphosphate Receptors, Male, Methoxyhydroxyphenylglycol, Mice, Inbred C57BL, Neurons, Patch-Clamp Techniques, Protein Binding, Protein Isoforms |
| الوصف: | Canonical transient receptor potential (TRPC3) nonselective cation channels are effectors of G-protein-coupled receptors (GPCRs), activated via phospholipase C–diacylglycerol signaling. In cerebellar Purkinje cells, TRPC3 channels cause the metabotropic glutamate receptor (mGluR)-mediated slow EPSC (sEPSC). TRPC3 channels also provide negative feedback regulation of cytosolic Ca2 , mediated by a C terminus “calmodulin and inositol trisphosphate receptor binding” (CIRB) domain. Here we report the alternative splicing of the TRPC3mRNAtranscript (designated TRPC3c), resulting in omission of exon 9 (approximately half of the CIRB domain) in mice, rats, and guinea pigs. TRPC3c expression is brain region specific, with prevalence in the cerebellum and brainstem. The TRPC3c channels expressed in HEK293 cells exhibit increased basal and GPCR-activated channel currents, and increased Ca2 fluorescence responses, compared with the previously characterized (TRPC3b) isoform when activated via either the endogenous M3 muscarinic acetylcholine receptor, or via coexpressed mGluR1. GPCR-induced TRPC3c channel opening rate (cell-attached patch) matched the maximum activation achieved with inside-out patches with zero cytosolic Ca2+, whereas the GPCR-induced TRPC3b activation frequency was significantly less. Both TRPC3 channel isoforms were blocked with 2mM Ca2+, attributable to CIRB domain regulation. In addition, genistein blocked Purkinje cell (S)-2-amino-2-(3,5-dihydroxyphenyl) acetic acid (mGluR1)-activated TPRC3 current as for recombinant TRPC3c current. This novel TRPC3c ion channel therefore has enhanced efficacy as a neuronal GPCR-Ca2+ signaling effector, and is associated with sensorimotor coordination, neuronal development, and brain injury. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | http://hdl.handle.net/1959.4/unsworks_43535Test; https://unsworks.unsw.edu.au/bitstreams/99f6fbeb-4cba-4ce5-9ca9-e0dde380f653/downloadTest; https://doi.org/10.1523/JNEUROSCI.6446-11.2012Test |
| DOI: | 10.1523/JNEUROSCI.6446-11.2012 |
| الإتاحة: | https://doi.org/10.1523/JNEUROSCI.6446-11.2012Test http://hdl.handle.net/1959.4/unsworks_43535Test https://unsworks.unsw.edu.au/bitstreams/99f6fbeb-4cba-4ce5-9ca9-e0dde380f653/downloadTest |
| حقوق: | open access ; https://purl.org/coar/access_right/c_abf2Test ; CC-BY-NC-ND ; https://creativecommons.org/licenses/by-nc-nd/4.0Test/ ; CC BY-NC-SA ; https://creativecommons.org/licenses/by-nc-sa/4.0Test/ ; free_to_read |
| رقم الانضمام: | edsbas.7C310395 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1523/JNEUROSCI.6446-11.2012 |
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