Effect of protein kinase C activation on the glycine evoked Cl super(-) current in spinal cord neurons

We investigated whether the effect of phorbol-12-myristate-13-acetate (PMA) was altered by a kinase inhibitor and by down-regulation of protein kinase C (PKC) in order to determine if glycine receptors in mouse spinal neurons, unlike those in hippocampal and trigeminal neurons, can be inhibited by P...

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Bibliographic Details
Published in:Brain research 2001-05, Vol.902 (1), p.1-10
Main Authors: Albarran, F A, Roa, J P, Navarrete, R, Castillo, R, Nualart, F, Aguayo, L G
Format: Article
Language:English
Subjects:
phorbol 12-myristate 13-acetate
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Summary:We investigated whether the effect of phorbol-12-myristate-13-acetate (PMA) was altered by a kinase inhibitor and by down-regulation of protein kinase C (PKC) in order to determine if glycine receptors in mouse spinal neurons, unlike those in hippocampal and trigeminal neurons, can be inhibited by PKC. To examine the above, electrophysiological and immunofluorescence studies were carried out in mouse spinal neurons kept in culture for up to 3 weeks. The inhibition of the glycine activated current by PMA (1 mu M) increased from 12 plus or minus 3% during week 1 to 27 plus or minus 6% during week 3. The effect of PMA was completely blocked by the PKC selective inhibitor RO 31-8220 (1 mu M). After culturing the cells with 1 mu M PMA for 24 h, the inhibitory effect of acute application of PMA disappeared altogether, suggesting that the effect of PMA was via PKC. Immunofluorescence studies showed that a short stimulation with PMA translocated the enzyme to the periphery whereas longer term stimulation (24 h) down regulated the PKC signal. These results indicate that activation of PKC by PMA inhibits the glycine receptor in cultured spinal neurons and that its sensitivity changes during neuronal development.
ISSN:0006-8993