Excitatory Roles of Protein Kinase C in Striatal Cholinergic Interneurons

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American Physiological Society

RESUMO

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 PKCα, but not PKCγ and PKCε, 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 PKCα, 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.

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