TY - JOUR T1 - Ca<sup>2+</sup> Regulation of Ca<sub>v</sub>3.3 T-type Ca<sup>2+</sup> Channel Is Mediated by Calmodulin JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.117.108530 SP - mol.117.108530 AU - Narae Lee AU - Sua Jeong AU - Kang-Chang Kim AU - Jin-Ah Kim AU - Jin-Yong Park AU - Ho-Won Kang AU - Edward Perez-Reyes AU - Jung-Ha Lee Y1 - 2017/01/01 UR - http://molpharm.aspetjournals.org/content/early/2017/07/07/mol.117.108530.abstract N2 - 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. ER -