| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received October 22, 2002
Accepted after revision December 12, 2002
1 Department of Biomedical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK
2 Pfizer Global Research and Development, Cambridge Research Site, Robinson Way, Cambridge CB2 1QB, UK
3 Department of Pharmacology and Neuroscience, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK
* To whom correspondence should be addressed. E-mail: m.l.j.ashford{at}dundee.ac.uk.
Striatal neurones are particularly vulnerable to hypoxia/ischaemia-induced damage, and free radicals are thought to be prime mediators of this neuronal destruction. It has been shown that hydrogen peroxide (H2O2), through the production of free radicals, induces rat insulinoma cell death by activation of a non-selective cation channel, which leads to irreversible cell depolarization and unregulated Ca2+ entry into the cell. In the study presented here, we demonstrate that a subpopulation of striatal neurones (medium spiny neurones) is depolarized by H2O2 through the production of free radicals. Cell-attached recordings from rat cultured striatal neurones demonstrate that exposure to H2O2 opens a large-conductance channel that is characterized by extremely long open times (seconds). Inside-out recordings show that cytoplasmically applied 
-nicotinamide adenine dinucleotide activates a channel with little voltage dependence, a linear current-voltage relationship and a single-channel conductance of between 70 and 90 pS. This channel is permeable to Na+, K+ and Ca2+ ions. Fura-2 imaging from cultured striatal neurones reveal that H2O2 exposure induces a biphasic intracellular Ca2+ increase in a subpopulation of neurones, the second, later phase resulting in Ca2+ overload. This later component of the Ca2+ response is dependent on the presence of extracellular Ca2+ and is independent of synaptic activity or voltage-gated Ca2+ channel opening. Consequently, this channel may be an important contributor to free-radical-induced selective striatal neurone destruction. These results are remarkably similar to those observed for insulinoma cells and suggest that this family of non-selective cation channels has a widespread distribution in mammalian tissues.
This article has been cited by other articles:
|
|
 |
|
  D. A. Lupinsky and N. S. Magoski Ca2+-dependent regulation of a non-selective cation channel from Aplysia bag cell neurones J. Physiol., September 1, 2006; 575(2): 491 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Grubisha, L. A. Rafty, C. L. Takanishi, X. Xu, L. Tong, A.-L. Perraud, A. M. Scharenberg, and J. M. Denu Metabolite of SIR2 Reaction Modulates TRPM2 Ion Channel J. Biol. Chem., May 19, 2006; 281(20): 14057 - 14065. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Hong, S. J. Moon, H. M. Byun, M. S. Kim, H. Jo, Y. S. Bae, S.-I. Lee, M. D. Bootman, H. L. Roderick, D. M. Shin, et al. Critical Role of Phospholipase C{gamma}1 in the Generation of H2O2-evoked [Ca2+]i Oscillations in Cultured Rat Cortical Astrocytes J. Biol. Chem., May 12, 2006; 281(19): 13057 - 13067. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Bao, M. V. Avshalumov, and M. E. Rice Partial Mitochondrial Inhibition Causes Striatal Dopamine Release Suppression and Medium Spiny Neuron Depolarization via H2O2 Elevation, Not ATP Depletion J. Neurosci., October 26, 2005; 25(43): 10029 - 10040. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kraft, C. Grimm, K. Grosse, A. Hoffmann, S. Sauerbruch, H. Kettenmann, G. Schultz, and C. Harteneck Hydrogen peroxide and ADP-ribose induce TRPM2-mediated calcium influx and cation currents in microglia Am J Physiol Cell Physiol, January 1, 2004; 286(1): C129 - C137. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
