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.