کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6021933 | 1580655 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Mechanism underlying unaltered cortical inhibitory synaptic transmission in contrast with enhanced excitatory transmission in CaV2.1 knockin migraine mice
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کلمات کلیدی
CSDfast-spiking interneuronFHM1BMEChannelopathyPBSCGRPSNAP25GADVIPLJPBSA - BSAglutamic acid decarboxylase - glutamic acid dearboxylasesiRNA - siRNASOM - WHObovine serum albumin - آلبومین سرم گاوsmall interfering ribonucleic acid - اسید ریبونوکلئیک دخالت کندgamma-aminobutyric acid - اسید گاما آمینو بوتیریکcortical spreading depression - افسردگی گسترش کورتکسDIV - دیوdays in vitro - روز in vitrofast-spiking - سریع اسپایکینگSomatostatin - سوماتواستاتینAHP - فرایند تحلیل سلسلهمراتبیPhosphate buffered saline - فسفات بافر شورbasal Eagle's medium - محیط عقاب پایهMigraine - میگرنKnockin - ناکینParvalbumin - پاروالبومینLiquid junction potential - پتانسیل اتصال مایعaction potential - پتانسیل عمل synaptosomal-associated protein of 25 kDa - پروتئین مرتبط با سیناپتوزومی 25 کیلو دالتونafter-hyperpolarization - پس از hyperpolarizationvasoactive intestinal peptide - پپتید روده روده ایcalcitonin gene-related peptide - پپتید مرتبط با ژن کلسی تونینGABA - گابا
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Familial hemiplegic migraine type 1 (FHM1), a monogenic subtype of migraine with aura, is caused by gain-of-function mutations in CaV2.1 (P/Q-type) calcium channels. In FHM1 knockin mice, excitatory neurotransmission at cortical pyramidal cell synapses is enhanced, but inhibitory neurotransmission at connected pairs of fast-spiking (FS) interneurons and pyramidal cells is unaltered, despite being initiated by CaV2.1 channels. The mechanism underlying the unaltered GABA release at cortical FS interneuron synapses remains unknown. Here, we show that the FHM1 R192Q mutation does not affect inhibitory transmission at autapses of cortical FS and other types of multipolar interneurons in microculture from R192Q knockin mice, and investigate the underlying mechanism. Lowering the extracellular [Ca2+] did not reveal gain-of-function of evoked transmission neither in control nor after prolongation of the action potential (AP) with tetraethylammonium, indicating unaltered AP-evoked presynaptic calcium influx at inhibitory autapses in FHM1 KI mice. Neither saturation of the presynaptic calcium sensor nor short duration of the AP can explain the unaltered inhibitory transmission in the mutant mice. Recordings of the P/Q-type calcium current in multipolar interneurons in microculture revealed that the current density and the gating properties of the CaV2.1 channels expressed in these interneurons are barely affected by the FHM1 mutation, in contrast with the enhanced current density and left-shifted activation gating of mutant CaV2.1 channels in cortical pyramidal cells. Our findings suggest that expression of specific CaV2.1 channels differentially sensitive to modulation by FHM1 mutations in inhibitory and excitatory cortical neurons underlies the gain-of-function of excitatory but unaltered inhibitory synaptic transmission and the likely consequent dysregulation of the cortical excitatory-inhibitory balance in FHM1.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 69, September 2014, Pages 225-234
Journal: Neurobiology of Disease - Volume 69, September 2014, Pages 225-234
نویسندگان
Dania Vecchia, Angelita Tottene, Arn M.J.M. van den Maagdenberg, Daniela Pietrobon,