Channelpedia

PubMed 18298939


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Cav2.2



Title: PMA counteracts G protein actions on CaV2.2 channels in rat sympathetic neurons.

Authors: Alfonso F Díaz-Cárdenas, Isabel Arenas, David E García

Journal, date & volume: Arch. Biochem. Biophys., 2008 May 1 , 473, 1-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18298939


Abstract
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 GTPgammaS-induced I(Ca) inhibition, but also reverses current inhibition by Gbetagamma 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 GDPbetaS. 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.