ISSN:
1600-079X
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: Activation of K+ current plays a critical role in the control of programmed cell death. In the present study, whole-cell patch-clamp recording, a caspase-3 activity assay, and flow cytometric analysis were used to examine the effects of the MT2 melatonin receptor agonist 2-iodomelatonin on the delayed-rectifier K+ current (IK) and the prevention of apoptosis. It was found that apoptosis of cerebellar granular neurons induced by low-K+ (5 mm) incubation was associated with an increase in IK amplitude and caspase-3 activity. After 6 hr of low-K+ treatment, IK was increased by 45% (n = 86). Flow cytometry showed that the apoptosis rate increased by 333% compared with the control neurons. In addition, exposure of cultured granule cells to low K+ also resulted in a significant activation of caspase-3, by 466%. 2-Iodomelatonin (10 μm in injection pipette) inhibited the IK amplitude recorded from control cells and from cells undergoing apoptosis. However, 2-iodomelatonin only modified the IK-channel activation kinetics of cells under both conditions. Furthermore, 2-iodomelatonin reduced the rate of apoptosis and caspase-3 activation, by 66 and 64%, respectively. The melatonin receptor antagonist, 4P-PDOT, abrogated the effect of 2-iodomelatonin on the IK augmentation, caspase-3 activity, and apoptosis. These results suggest that the neuroprotective effects of melatonin are not only because of its function as a powerful antioxidant, but also to its interactions with specific receptors. The effect of 2-iodomelatonin against apoptosis may be mediated by activating a melatonin receptor, which modulates IK channels and reduces K+ efflux.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1600-079X.2003.00104.x
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