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J Neurophysiol 102: 2453-2461, 2009. First published August 5, 2009; doi:10.1152/jn.00325.2009
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RESEARCH-ARTICLE

Excitatory Roles of Protein Kinase C in Striatal Cholinergic Interneurons

Ping Deng, Zhi-Ping Pang, Zhigang Lei and Zao C. Xu

Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana

Submitted 9 April 2009; accepted in final form 4 August 2009

ABSTRACT

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 (IA), 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 IA with potassium channel blocker 4-aminopyridine. In addition, immunostaining demonstrated that PKC{alpha}, but not PKC{gamma} and PKC{varepsilon}, was expressed in cholinergic interneurons. Furthermore, activation of group I metabotropic glutamate receptors (mGluRs) led to an inhibition of IA through a PKC-dependent pathway. These data indicate that activation of PKC, most likely PKC{alpha}, increases the neuronal excitability of striatal cholinergic interneurons by down-regulating IA. Group I mGluR-mediated IA inhibition might be important for the glutamatergic regulation of cholinergic tone in the neostriatum.


Address for reprint requests and other correspondence: Z. C. Xu, Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Drive, MS 507, Indianapolis, IN 46202 (E-mail: zxu{at}anatomy.iupui.edu).







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