Author:
Xie Yu-Feng,Belrose Jillian C,Lei Gang,Tymianski Michael,Mori Yasuo,MacDonald John F,Jackson Michael F
Abstract
Abstract
Transient receptor potential melastatin 2 (TRPM2) is a calcium permeable non-selective cation channel that functions as a sensor of cellular redox status. Highly expressed within the CNS, we have previously demonstrated the functional expression of these channels in CA1 pyramidal neurons of the hippocampus. Although implicated in oxidative stress-induced neuronal cell death, and potentially in neurodegenerative disease, the physiological role of TRPM2 in the central nervous system is unknown. Interestingly, we have shown that the activation of these channels may be sensitized by co-incident NMDA receptor activation, suggesting a potential contribution of TRPM2 to synaptic transmission. Using hippocampal cultures and slices from TRPM2 null mice we demonstrate that the loss of these channels selectively impairs NMDAR-dependent long-term depression (LTD) while sparing long-term
potentiation. Impaired LTD resulted from an inhibition of GSK-3β, through increased phosphorylation, and a reduction in the expression of PSD95 and AMPARs. Notably, LTD could
be rescued in TRPM2 null mice by recruitment of GSK-3β signaling following dopamine D2 receptor stimulation. We propose that TRPM2 channels play a key role in hippocampal synaptic plasticity.
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Molecular Biology
Reference21 articles.
1. Takahashi N, Kozai D, Kobayashi R, Ebert M, Mori Y: Roles of TRPM2 in oxidative stress. Cell Calcium. 2011
2. Xie YF, Macdonald JF, Jackson MF: TRPM2, calcium and neurodegenerative diseases. Int J Physiol Pathophysiol Pharmacol. 2010, 2 (2): 95-103.
3. Olah ME, Jackson MF, Li H, Perez Y, Sun HS, Kiyonaka S, Mori Y, Tymianski M, MacDonald JF: Ca2+-dependent induction of TRPM2 currents in hippocampal neurons. J Physiol. 2009, 587 (Pt 5): 965-979.
4. Scharenberg AM: TRPM2 and TRPM7: channel/enzyme fusions to generate novel intracellular sensors. Pflugers Arch. 2005, 451 (1): 220-227. 10.1007/s00424-005-1444-0.
5. Yamamoto S, Shimizu S, Kiyonaka S, Takahashi N, Wajima T, Hara Y, Negoro T, Hiroi T, Kiuchi Y, Okada T, Kaneko S, Lange I, Fleig A, Penner R, Nishi M, Takeshima H, Mori Y: TRPM2-mediated Ca2+influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration. Nat Med. 2008, 14 (7): 738-747. 10.1038/nm1758.
Cited by
58 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献