%0 Journal Article %A Narae Lee %A Sua Jeong %A Kang-Chang Kim %A Jin-Ah Kim %A Jin-Yong Park %A Ho-Won Kang %A Edward Perez-Reyes %A Jung-Ha Lee %T Ca2+ Regulation of Cav3.3 T-type Ca2+ Channel Is Mediated by Calmodulin %D 2017 %R 10.1124/mol.117.108530 %J Molecular Pharmacology %P mol.117.108530 %X Numerous investigations reported that increases of internal Ca2+ (Ca2+i) pivotally regulate high voltage-activated (HVA) Ca2+ channels via calmodulin (CaM). However, it is largely elusive that Ca2+i can regulate low voltage-activated T-type Ca2+ channels. Using whole cell patch clamp, we compared the biophysical properties of Ca2+ current through T-type Ca2+ channel Cav3.1, Cav3.2, or Cav3.3 stably expressed in HEK293 cells between internal solutions containing 27 nM and l μM free Ca2+. Both activation and inactivation kinetics of Cav3.3 current in l μM Ca2+i solution were more rapid than those of Cav3.3 in 27 nM Ca2+i solution. In addition, both activation and steady-state inactivation curves of Cav3.3 were negatively shifted in the higher Ca2+i solution. In contrast, the biophysical properties of Cav3.1 and Cav3.2 isoforms were not different between the two internal solutions. Overexpression of CaM1234 (calmodulin mutant lacking 4 Ca2+ binding sites) strongly suppressed the effects of l μM Ca2+i on Cav3.3, implying that CaM is involved in the Ca2+i regulation effects on Cav3.3. Yeast two hybrid screenings and coimmunoprecipitation experiments revealed direct interaction of the carboxyl terminus of Cav3.3 with CaM. Taken together, our results suggest that Cav3.3 T-type channel is be potently regulated by Ca2+i via interaction of Ca2+/CaM with the carboxyl terminus of Cav3.3. %U https://molpharm.aspetjournals.org/content/molpharm/early/2017/07/07/mol.117.108530.full.pdf