dc.contributor.author |
Chung, Kenny |
en |
dc.contributor.author |
Freestone, Peter |
en |
dc.contributor.author |
Lipski, Janusz |
en |
dc.coverage.spatial |
United States |
en |
dc.date.accessioned |
2012-02-17T00:22:12Z |
en |
dc.date.issued |
2011-12-01 |
en |
dc.identifier.citation |
J Neurophysiol 106(6):2865-2875 Dec 2011 |
en |
dc.identifier.issn |
0022-3077 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/11463 |
en |
dc.description.abstract |
Transient receptor potential melastatin 2 (TRPM2) channels are sensitive to oxidative stress, and their activation can lead to cell death. Although these channels have been extensively studied in expression systems, their role in the brain, particularly in the substantia nigra pars compacta (SNc), remains unknown. In this study, we assessed the expression and functional properties of TRPM2 channels in rat dopaminergic SNc neurons, using acute brain slices. RT-PCR analysis revealed TRPM2 mRNA expression in the SNc region. Immunohistochemistry demonstrated expression of TRPM2 protein in tyrosine hydroxylase-positive neurons. Channel function was tested with whole cell patch-clamp recordings and calcium (fura-2) imaging. Intracellular application of ADP-ribose (50-400 μM) evoked a dose-dependent, desensitizing inward current and intracellular free calcium concentration ([Ca(2+)](i)) rise. These responses were strongly inhibited by the nonselective TRPM2 channel blockers clotrimazole and flufenamic acid. Exogenous application of H(2)O(2) (1-5 mM) evoked a rise in [Ca(2+)](i) and an outward current mainly due to activation of ATP-sensitive potassium (K(ATP)) channels. Inhibition of K(+) conductance with Cs(+) and tetraethylammonium unmasked an inward current. The inward current and/or [Ca(2+)](i) rise were partially blocked by clotrimazole and N-(p-amylcinnamoyl)anthranilic acid (ACA). The H(2)O(2)-induced [Ca(2+)](i) rise was abolished in "zero" extracellular Ca(2+) concentration and was enhanced at higher baseline [Ca(2+)](i), consistent with activation of TRPM2 channels in the cell membrane. These results provide evidence for the functional expression of TRPM2 channels in dopaminergic SNc neurons. Given the involvement of oxidative stress in degeneration of SNc neurons in Parkinson's disease, further studies are needed to determine the pathophysiological role of these channels in the disease process. |
en |
dc.language |
eng |
en |
dc.relation.ispartofseries |
Journal of Neurophysiology |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/0022-3077/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
Adenosine Diphosphate Ribose |
en |
dc.subject |
Adenosine Triphosphate |
en |
dc.subject |
Animals |
en |
dc.subject |
Biophysics |
en |
dc.subject |
Calcium |
en |
dc.subject |
Clusterin |
en |
dc.subject |
Dopaminergic Neurons |
en |
dc.subject |
Dose-Response Relationship, Drug |
en |
dc.subject |
Electric Stimulation |
en |
dc.subject |
Excitatory Amino Acid Antagonists |
en |
dc.subject |
Gene Expression Regulation |
en |
dc.subject |
Glyburide |
en |
dc.subject |
Hydrogen Peroxide |
en |
dc.subject |
Isoquinolines |
en |
dc.subject |
Membrane Potentials |
en |
dc.subject |
Oxidants |
en |
dc.subject |
Patch-Clamp Techniques |
en |
dc.subject |
Piperidines |
en |
dc.subject |
Potassium Channel Blockers |
en |
dc.subject |
RNA, Messenger |
en |
dc.subject |
Rats |
en |
dc.subject |
Reactive Oxygen Species |
en |
dc.subject |
Substantia Nigra |
en |
dc.subject |
Tetraethylammonium |
en |
dc.subject |
Tolbutamide |
en |
dc.subject |
Tyrosine 3-Monooxygenase |
en |
dc.title |
Expression and functional properties of TRPM2 channels in dopaminergic neurons of the substantia nigra of the rat |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1152/jn.00994.2010 |
en |
pubs.issue |
6 |
en |
pubs.begin-page |
2865 |
en |
pubs.volume |
106 |
en |
dc.identifier.pmid |
21900507 |
en |
pubs.author-url |
http://www.ncbi.nlm.nih.gov/pubmed/21900507 |
en |
pubs.end-page |
2875 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
239846 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Physiology Division |
en |
dc.identifier.eissn |
1522-1598 |
en |
dc.identifier.pii |
jn.00994.2010 |
en |
pubs.record-created-at-source-date |
2013-06-05 |
en |
pubs.dimensions-id |
21900507 |
en |