Ncrease of Delayed Rectifier Potassium Currents in Arge Aspiny Neurons in the Neostriatum following Ransient Forebrain Ischemia

bstract —Large aspiny (LA) neurons in the neostriatum are esistant to cerebral ischemia whereas spiny neurons are ighly vulnerable to the same insult. Excitotoxicity has been mplicated as the major cause of neuronal damage after ischmia. Voltage-dependent potassium currents play important oles in controlling neuronal excitability and therefore influnce the ischemic outcome. To reveal the ionic mechanisms nderlying the ischemia-resistance, the delayed rectifier poassium currents (Ik) in LA neurons were studied before and t different intervals after transient forebrain ischemia using rain slices and acute dissociation preparations. The current ensity of Ik increased significantly 24 h after ischemia and eturned to control levels 72 h following reperfusion. Among urrents contributing to Ik, the margatoxin-sensitive currents ncreased 24 h after ischemia while the KCNQ/M current reained unchanged after ischemia. Activation of protein kiase A (PKA) down-regulated Ik in both control and ischemic A neurons, whereas inhibition of PKA only up-regulated Ik nd margatoxin-sensitive currents 72 h after ischemia, indiating an active PKA regulation on Ik at this time. Protein yrosine kinases had a tonic inhibition on Ik to a similar extent efore and after ischemia. Compared with that of control eurons, the spike width was significantly shortened 24 h fter ischemia due to facilitated repolarization, which could e reversed by blocking margatoxin-sensitive currents. The ncrease of Ik in LA neurons might be one of the protective echanisms against ischemic insult. © 2005 IBRO. Published y Elsevier Ltd. All rights reserved.