Direct interaction and functional coupling between voltage-gated CaV1.3 Ca2+ channel and GABAB receptor subunit 2.
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.
Park
Hye-Won
HW
Life Sciences Division, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
Jung
Hana
H
Choi
Kee-Hyun
KH
Baik
Ja-Hyun
JH
Rhim
Hyewhon
H
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D002460:Cell Line; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D015640:Ion Channel Gating; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D015220:Calcium Channels; C116566:Gabbr2 protein, rat; D021122:Protein Subunits; D018080:Receptors, GABA-B; C093712:Cacna1d protein, rat