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Neuroscience. 2005;131(1):135-46.

Increase of delayed rectifier potassium currents in large aspiny neurons in the neostriatum following transient forebrain ischemia.

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Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Drive, MS 507, Indianapolis, IN 46202, USA.


Large aspiny (LA) neurons in the neostriatum are resistant to cerebral ischemia whereas spiny neurons are highly vulnerable to the same insult. Excitotoxicity has been implicated as the major cause of neuronal damage after ischemia. Voltage-dependent potassium currents play important roles in controlling neuronal excitability and therefore influence the ischemic outcome. To reveal the ionic mechanisms underlying the ischemia-resistance, the delayed rectifier potassium currents (Ik) in LA neurons were studied before and at different intervals after transient forebrain ischemia using brain slices and acute dissociation preparations. The current density of Ik increased significantly 24 h after ischemia and returned to control levels 72 h following reperfusion. Among currents contributing to Ik, the margatoxin-sensitive currents increased 24 h after ischemia while the KCNQ/M current remained unchanged after ischemia. Activation of protein kinase A (PKA) down-regulated Ik in both control and ischemic LA neurons, whereas inhibition of PKA only up-regulated Ik and margatoxin-sensitive currents 72 h after ischemia, indicating an active PKA regulation on Ik at this time. Protein tyrosine kinases had a tonic inhibition on Ik to a similar extent before and after ischemia. Compared with that of control neurons, the spike width was significantly shortened 24 h after ischemia due to facilitated repolarization, which could be reversed by blocking margatoxin-sensitive currents. The increase of Ik in LA neurons might be one of the protective mechanisms against ischemic insult.

[Indexed for MEDLINE]

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