Striatal cholinergic interneurons are relatively resistant to ischemic insults. These neurons express hyperpolarization-activated cation current (Ih) that profoundly regulates neuronal excitability. Changes in neuronal excitability early after ischemia may be crucial for determining neuronal injury. Here we report that Ih 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 Ih might be due to the tonic activation of adenosine A1 receptors, as blockade of A1 receptors significantly increased Ih in postischemic neurons, but had no effect on control neurons. Consistent with the inhibition of Ih, postischemic neurons showed a reduction in both spontaneous firing and hyperpolarization-induced rebound depolarization. These findings indicate that Ih may play excitatory roles in striatal cholinergic interneurons. Postischemic inhibition of Ih might be a novel mechanism by which adenosine confers neuronal resistance to cerebral ischemia.
- Basal ganglia
- Cyclic AMP
- Rebound depolarization
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism