Inhibition of Ih in Striatal Cholinergic Interneurons Early after Transient Forebrain Ischemia

Abstract

Striatal cholinergic interneurons are relatively resistant to ischemic insults. These neurons express hyperpolarization-activated cation current ( I_h) that profoundly regulates neuronal excitability. Changes in neuronal excitability early after ischemia may be crucial for determining neuronal injury. Here we report that I_h in cholinergic interneurons was decreased 3 h after transient forebrain ischemia, which was accompanied by a negative shift of the voltage dependence of activation. The inhibition of I_h might be due to the tonic activation of adenosine A1 receptors, as blockade of A1 receptors significantly increased I_h in postischemic neurons, but had no effect on control neurons. Consistent with the inhibition of I_h, postischemic neurons showed a reduction in both spontaneous firing and hyperpolarization-induced rebound depolarization. These findings indicate that I_h may play excitatory roles in striatal cholinergic interneurons. Postischemic inhibition of I_h might be a novel mechanism by which adenosine confers neuronal resistance to cerebral ischemia.