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

Abstract

Although CaV1.2 and CaV1.3 are two subtypes of L-type Ca2+ channels expressed in the CNS, functions of CaV1.3 have not been well elucidated compared to CaV1.2. Here, we found that CaV1.3-NT associates with GABABR2-CT using yeast two-hybrid, GST pull-down and co-immunoprecipitation assays. We also demonstrated co-localization of CaV1.3 and GABABR2 in HEK293 cells and cultured hippocampal neurons. Whole-cell patch-clamp and Ca2+-imaging experiments revealed that activation of GABABR increases CaV1.3 currents and intracellular Ca2+ via CaV1.3, but not CaV1.2. These results show a physical and functional interaction between CaV1.3 and GABABR, suggesting the potential pivotal roles of CaV1.3 in the CNS.