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[摘要]：Protein kinase C (PKC)-induced phosphorylation and G protein-mediated inhibition of Ca(v)2.2 N-type Ca2+ channels counteract exerting opposing modulatory responses at the channel level. At present, the most striking question remaining is whether prominent enhancement of the Ca2+ current (I-Ca) observed under PKC activation arises from relief of G-protein tonic inhibition. Here, by using patch-clamp methods in superior cervical ganglion (SCG) neurons of rat, we show the following: First, that PKC activation by phorbol-12-myristate- 13 -acetate (PMA) not only counteracts mutually with noradrenaline (NA) and GTP gamma S-induced I-Ca inhibition, but also reverses current inhibition by G beta gamma subunits over-expression. Second, that PMA increases I-Ca, beyond the enhancement expected by sole removal of the G protein-mediated tonic inhibition. Accordingly, PMA increases conductance through N-type Ca2+ channels, unlike the G protein inhibitor GDPPS. Together, our results support that PMA-induced phosphorylation produces changes in I-Ca that cannot be accounted for by prevention of G protein inhibition. They may have important implications in reinterpretation of existing data with PMA. Furthermore, counteracting modulation of ion channels and reversibility within a short time frame are better support for a dynamic system with short-term adaptive responses.(c) 2008 Elsevier Inc. All rights reserved. |
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