Direct interaction and functional coupling between voltage-gated Ca(v)1.3 Ca2+ channel and GABA(B) receptor subunit 2

Abstract

Although Ca(v)1.2 and Ca(v)1.3 are two subtypes of L-type Ca2+ channels expressed in the CNS, functions of Ca(v)1.3 have not been well elucidated compared to Ca(v)1.2. Here, we found that Ca(v)1.3-NT associates with GABA(B)R2-CT using yeast two-hybrid, GST pull-down and co-immunoprecipitation assays. We also demonstrated co-localization of Ca(v)1.3 and GABA(B)R2 in HEK293 cells and cultured hippocampal neurons. Whole-cell patch-clamp and Ca2+-imaging experiments revealed that activation of GABA(B)R increases Ca(v)1.3 currents and intracellular Ca2+ via Ca(v)1.3, but not Ca(v)1.2. These results show a physical and functional interaction between Ca(v)1.3 and GABA(B)R, suggesting the potential pivotal roles of Ca(v)1.3 in the CNS. Structured summary: MINT-7975667: Ca(v)1.3 (uniprotkb:P27732) physically interacts (MI:0915) with GABA(B)R2 (uniprotkb:088871) by two hybrid (MI:0018) MINT-7975740: Ca(v)1.3 (uniprotkb:P27732) and GABA(B)R2 (uniprotkb:075899) colocalize (MI:0403) by fluorescence microscopy (MI:0416) MINT-7966007, MINT-7966016: Ca(v)1.3 (uniprotkb:P27732) physically interacts (MI :0915) with GABA(B)R2 (uniprotkb:088871) by anti bait coimmunoprecipitation (MI:0006) MINT-7975712, MINT-7975691: Ca(v)1.3 (uniprotkb:P27732) physically interacts (MI:0915) with GABA(B)R2 (uniprotkb:088871) by pull down (MI:0096) MINT-7966026: GABA(B)R2 (uniprotkb:088871) and Ca(v)1.3 (uniprotkb:P27732) colocalize (MI:0403) by fluorescence microscopy (MI:0416) (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.