Résumé
Modulation of low voltage-activated Ca sub(V)3 T-type calcium channels remains poorly characterized compared with high voltage-activated Ca sub(V)1 and Ca sub(V)2 calcium channels. Notably, it is yet unresolved whether Ca sub(V)3 channels are modulated by protein kinases in mammalian cells. In this study, we demonstrate that protein kinase A (PKA) and PKC (but not PKG) activation induces a potent increase in Ca sub(V)3.1, Ca sub(V)3.2, and Ca sub(V)3.3 currents in various mammalian cell lines. Notably, we show that protein kinase effects occur at physiological temperature ( similar to 30-37 degree C) but not at room temperature ( similar to 22-27 degree C). This temperature dependence could involve kinase translocation, which is impaired at room temperature. A similar temperature dependence was observed for PKC-mediated increase in high voltage-activated Ca sub(V)2.3 currents. We also report that neither Ca sub(V)3 surface expression nor T-current macroscopic properties are modified upon kinase activation. In addition, we provide evidence for the direct phosphorylation of Ca sub(V)3.2 channels by PKA in in vitro assays. Overall, our results clearly establish the role of PKA and PKC in the modulation of Ca sub(V)3 T-channels and further highlight the key role of the physiological temperature in the effects described.