کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4340304 | 1295789 | 2009 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Signaling mechanisms mediating muscarinic enhancement of GABAergic synaptic transmission in the spinal cord
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کلمات کلیدی
Trp[3H]QNBmAChRGDP-β-S[3H]quinuclidinyl benzilatesIPSCsaCSFPI3Kguanosine 5′-O-(2-thiodiphosphate) - guanosine 5'-O- (2-thiodiphosphate)Small interfering RNA - RNA تداخل کوچکsiRNA - siRNAadenylyl cyclase - آدنیلات سیکلاز، آدنیلیل سیکلازAcetylcholine - استیل کولینSpontaneous inhibitory postsynaptic currents - جریانهای پسینپتیک مهار کننده خود به خودیdorsal horn - شاخ پشتیSpinal cord - طناب نخاعیphosphoinositide-3-kinase - فسفونیوییدید-3-کینازartificial cerebrospinal fluid - مایع مغزی نخاعی مصنوعیtransient receptor potential - پتانسیل گیرنده گذراnonselective cation channels - کانتین های غیر کیهانیGABA - گاباmuscarinic acetylcholine receptor - گیرنده استیل کولین muscarinicMuscarinic receptors - گیرنده های Muscarinic
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Activation of muscarinic acetylcholine receptors (mAChRs) inhibits spinal nociceptive transmission by potentiation of GABAergic tone through M2, M3, and M4 subtypes. To study the signaling mechanisms involved in this unique mAChR action, GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) of lamina II neurons were recorded using whole-cell patch clamp techniques in rat spinal cord slices. The mAChR agonist oxotremorine-M caused a profound increase in the frequency of GABAergic sIPSCs, which was abolished in the Ca2+-free solution. Inhibition of voltage-gated Ca2+ channels with Cd2+ and Ni2+ largely reduced the effect of oxotremorine-M on sIPSCs. Blocking nonselective cation channels (NSCCs) with SKF96365 or 2-APB also largely attenuated the effect of oxotremorine-M. However, the KCNQ channel blocker XE991 and the adenylyl cyclase inhibitor MDL12330A had no significant effect on oxotremorine-M-induced increases in sIPSCs. Furthermore, the phosphoinositide-3-kinase (PI3K) inhibitor wortmannin or LY294002 significantly reduced the potentiating effect of oxotremorine-M on sIPSCs. In the spinal cord in which the M3 subtype was specifically knocked down by intrathecal small interfering RNA (siRNA) treatment, SKF96365 and wortmannin still significantly attenuated the effect of oxotremorine-M. In contrast, SKF96365 and wortmannin both failed to alter the effect of oxotremorine-M on sIPSCs when the M2/M4 mAChRs were blocked. Therefore, our study provides new evidence that activation of mAChRs increases synaptic GABA release through Ca2+ influx and voltage-gated Ca2+ channels. The PI3K-NSCC signaling cascade is primarily involved in the excitation of GABAergic interneurons by the M2/M4 mAChRs in the spinal dorsal horn.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 158, Issue 4, 18 February 2009, Pages 1577-1588
Journal: Neuroscience - Volume 158, Issue 4, 18 February 2009, Pages 1577-1588
نویسندگان
H.-M. Zhang, S.-R. Chen, Y.-Q. Cai, T.E. Richardson, L.C. Driver, G. Lopez-Berestein, H.-L. Pan,