Inhibition of Ih in striatal cholinergic interneurons early after transient forebrain ischemia.
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.
Deng
Ping
P
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Zhang
Yuchun
Y
Xu
Zao C
ZC
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002317:Cardiovascular Agents / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000473:pathology / Q000502:physiology*; D003342:Corpus Striatum / Q000473:pathology / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D007395:Interneurons / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D020521:Stroke / Q000473:pathology / Q000503:physiopathology*
D002317:Cardiovascular Agents; D011743:Pyrimidines; D043682:Receptor, Adenosine A1; C082246:ICI D2788; D000242:Cyclic AMP; D002118:Calcium