(R)-roscovitine, a cyclin-dependent kinase inhibitor, enhances tonic GABA inhibition in rat hippocampus.
作者： A. Ivanov , R. Tyzio , Y. Zilberter , Yehezkel Ben-Ari
DOI: 10.1016/J.NEUROSCIENCE.2008.06.044
关键词:
摘要: Pharmacological agents that mediate a persistent GABAergic conductance are of considerable interest for treatment epilepsy. (R)-roscovitine is membrane permeable cyclin-dependent kinase inhibitor, designed to block cell division. It currently undergoing phase II clinical trial as an anticancer drug. We show increases tonic GABA-mediated current in rat hippocampal neurons. This enhanced appears independent synaptic GABA release and requires functional transmembrane transport. The effect associated with neither modification GABAA receptors nor protein activity, but significant increase intracellular concentration (R)-roscovitine-induced inhibition significantly suppresses spontaneous spiking activity pyramidal cells. Therefore, potent modulator neuronal hippocampus may provide tool preventing paroxysmal activity.
elsevier.com
sci-hub.se 参考文章(45)
Heidi L. Gaspary, Wengang Wang, George B. Richerson, Carrier-Mediated GABA Release Activates GABA Receptors on Hippocampal Neurons Journal of Neurophysiology. ,vol. 80, pp. 270- 281 ,(1998) , 10.1152/JN.1998.80.1.270
Donglin Bai, Guoyun Zhu, Peter Pennefather, Michael F. Jackson, John F. MacDonald, Beverley A. Orser, Distinct Functional and Pharmacological Properties of Tonic and Quantal Inhibitory Postsynaptic Currents Mediated by γ-Aminobutyric AcidA Receptors in Hippocampal Neurons Molecular Pharmacology. ,vol. 59, pp. 814- 824 ,(2001) , 10.1124/MOL.59.4.814
Zoltan Nusser, Istvan Mody, Selective Modulation of Tonic and Phasic Inhibitions in Dentate Gyrus Granule Cells Journal of Neurophysiology. ,vol. 87, pp. 2624- 2628 ,(2002) , 10.1152/JN.2002.87.5.2624
Sean B. Christie, Celia P. Miralles, Angel L. De Blas, GABAergic innervation organizes synaptic and extrasynaptic GABAA receptor clustering in cultured hippocampal neurons. The Journal of Neuroscience. ,vol. 22, pp. 684- 697 ,(2002) , 10.1523/JNEUROSCI.22-03-00684.2002
Alexey Semyanov, Matthew C. Walker, Dimitri M. Kullmann, GABA uptake regulates cortical excitability via cell type–specific tonic inhibition Nature Neuroscience. ,vol. 6, pp. 484- 490 ,(2003) , 10.1038/NN1043
George B. Richerson, Yuanming Wu, Dynamic equilibrium of neurotransmitter transporters: not just for reuptake anymore. Journal of Neurophysiology. ,vol. 90, pp. 1363- 1374 ,(2003) , 10.1152/JN.00317.2003
Jukka Jolkkonen, Maria Mazurkiewicz, Hannele Lahtinen, Paavo Riekkinen, Acute effects of γ-vinyl GABA on the GABAergic system in rats as studied by microdialysis European Journal of Pharmacology. ,vol. 229, pp. 269- 272 ,(1992) , 10.1016/0014-2999(92)90566-M
Jean Vautrin, Dragan Maric, Manana Sukhareva, Anne E. Schaffner, Jeffery L. Barker, Surface-accessible GABA supports tonic and quantal synaptic transmission. Synapse. ,vol. 37, pp. 38- 55 ,(2000) , 10.1002/(SICI)1098-2396(200007)37:1<38::AID-SYN5>3.0.CO;2-C
Adrian M. Senderowicz, Novel Small Molecule Cyclin-Dependent Kinases Modulators in Human Clinical Trials Cancer Biology & Therapy. ,vol. 2, pp. 83- 94 ,(2003) , 10.4161/CBT.207
A.Y. Valeyev, R.A. Cruciani, G.D. Lange, V.S. Smallwood, J.L. Barker, Cl− channels are randomly activated by continuous GABA secretion in cultured embryonic rat hippocampal neurons Neuroscience Letters. ,vol. 155, pp. 199- 203 ,(1993) , 10.1016/0304-3940(93)90707-R