دورية أكاديمية
Modulation of direct pathway striatal projection neurons by muscarinic M₄-type receptors.
| العنوان: | Modulation of direct pathway striatal projection neurons by muscarinic M₄-type receptors. |
|---|---|
| المؤلفون: | Hernández-Flores T; División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, PO Box 70-253, México City, DF 04510, Mexico., Hernández-González O; División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, PO Box 70-253, México City, DF 04510, Mexico., Pérez-Ramírez MB; División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, PO Box 70-253, México City, DF 04510, Mexico., Lara-González E; División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, PO Box 70-253, México City, DF 04510, Mexico., Arias-García MA; División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, PO Box 70-253, México City, DF 04510, Mexico., Duhne M; División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, PO Box 70-253, México City, DF 04510, Mexico., Pérez-Burgos A; División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, PO Box 70-253, México City, DF 04510, Mexico., Prieto GA; División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, PO Box 70-253, México City, DF 04510, Mexico., Figueroa A; División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, PO Box 70-253, México City, DF 04510, Mexico., Galarraga E; División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, PO Box 70-253, México City, DF 04510, Mexico., Bargas J; División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, PO Box 70-253, México City, DF 04510, Mexico. Electronic address: jbargas@ifc.unam.mx. |
| المصدر: | Neuropharmacology [Neuropharmacology] 2015 Feb; Vol. 89, pp. 232-44. Date of Electronic Publication: 2014 Oct 05. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Pergamon Press Country of Publication: England NLM ID: 0236217 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-7064 (Electronic) Linking ISSN: 00283908 NLM ISO Abbreviation: Neuropharmacology Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Pergamon Press Original Publication: Oxford, New York, Pergamon. |
| مواضيع طبية MeSH: | Corpus Striatum/*cytology , Neural Pathways/*physiology , Neurons/*physiology , Receptor, Muscarinic M4/*metabolism, Acetylcholine/pharmacology ; Animals ; Calcium Channel Blockers/pharmacology ; Cells, Cultured ; Dopamine/pharmacology ; In Vitro Techniques ; Male ; Membrane Potentials/drug effects ; Membrane Potentials/genetics ; Mice ; Mice, Transgenic ; Neural Pathways/drug effects ; Neurons/drug effects ; Nicardipine/pharmacology ; Receptors, Dopamine D1/genetics ; Receptors, Dopamine D2/genetics ; Sodium Channel Blockers/pharmacology ; Tetrodotoxin/pharmacology |
| مستخلص: | Models of basal ganglia (BG) function posit a dynamic balance between two classes of striatal projection neurons (SPNs): direct pathway neurons (dSPNs) that facilitate movements, and indirect pathway neurons (iSPNs) that repress movement execution. Two main modulatory transmitters regulate the output of these neurons: dopamine (DA) and acetylcholine (ACh). dSPNs express D1-type DA, M1-and M4-type ACh receptors, while iSPNs express D2-type DA and M1-type ACh receptors. Actions of M1-, D1-, and D2-receptors have been extensively reported, but we still ignore most actions of muscarinic M4-type receptors. Here, we used whole-cell recordings in acutely dissociated neurons, pharmacological tools such as mamba-toxins, and BAC D(1 or 2)-eGFP transgenic mice to show that activation of M4-type receptors with bath applied muscarine enhances Ca(2+)-currents through CaV1-channels in dSPNs and not in iSPNs. This action increases excitability of dSPNs after both direct current injection and synaptically driven stimulation. The increases in Ca(2+)-current and excitability were blocked specifically by mamba toxin-3, suggesting mediation via M4-type receptors. M4-receptor activation also increased network activity of dSPNs but not of iSPNs as seen with calcium-imaging techniques. Moreover, actions of D1-type and M4-type receptors may add to produce a larger enhancement of excitability of dSPNs or, paradoxically, oppose each other depending on the order of their activation. Possible implications of these findings are discussed. (Copyright © 2014 Elsevier Ltd. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Acetylcholine; Ca(V)1 Ca(2+)-channels; Excitability; Striatal projection neurons; Striatum |
| المشرفين على المادة: | 0 (Calcium Channel Blockers) 0 (Receptor, Muscarinic M4) 0 (Receptors, Dopamine D1) 0 (Receptors, Dopamine D2) 0 (Sodium Channel Blockers) 4368-28-9 (Tetrodotoxin) CZ5312222S (Nicardipine) N9YNS0M02X (Acetylcholine) VTD58H1Z2X (Dopamine) |
| تواريخ الأحداث: | Date Created: 20141008 Date Completed: 20150715 Latest Revision: 20141201 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.neuropharm.2014.09.028 |
| PMID: | 25290553 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder كن أول من يترك تعليقا!