Excitatory roles of protein kinase C in striatal cholinergic interneurons.
Protein kinase C (PKC) plays critical roles in neuronal activity and is widely expressed in striatal neurons. However, it is not clear how PKC activation regulates the excitability of striatal cholinergic interneurons. In the present study, we found that PKC activation significantly inhibited A-type potassium current (I(A)), but had no effect on delayed rectifier potassium currents. Consistently, application of PKC activator caused an increase of firing in response to depolarizing currents in cholinergic interneurons, which was persistent in the presence of both excitatory and inhibitory neurotransmission blockers. These excitatory effects of PKC could be partially mimicked and occluded by blockade of I(A) with potassium channel blocker 4-aminopyridine. In addition, immunostaining demonstrated that PKCalpha, but not PKCgamma and PKCepsilon, was expressed in cholinergic interneurons. Furthermore, activation of group I metabotropic glutamate receptors (mGluRs) led to an inhibition of I(A) through a PKC-dependent pathway. These data indicate that activation of PKC, most likely PKCalpha, increases the neuronal excitability of striatal cholinergic interneurons by down-regulating I(A). Group I mGluR-mediated I(A) inhibition might be important for the glutamatergic regulation of cholinergic tone in the neostriatum.
Deng
Ping
P
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Pang
Zhi-Ping
ZP
Lei
Zhigang
Z
Xu
Zao C
ZC
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D051668:Delayed Rectifier Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D015398:Signal Transduction
D051668:Delayed Rectifier Potassium Channels; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D015761:4-Aminopyridine; C087857:protein kinase C gamma; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D011188:Potassium