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Updated: Jul 11, 2026

Single-Cell Calcium Imaging for Studying the Activation of Calcium Ion Channels
Published on: December 13, 2024
Temperature-dependent modulation of CaV3 T-type calcium channels by protein kinases C and A in mammalian cells
Jean Chemin1, Alexandre Mezghrani, Isabelle Bidaud
1Département de Physiologie, Institut de Génomique Fonctionnelle, CNRS UMR 5203, INSERM U661, Universités de Montpellier 1 et 2, Institut Fédératif de Recherche 3, 141 Rue de la Cardonille, Montpellier, France. jean.chemin@igf.cnrs.fr
Abstract:
Modulation of low voltage-activated Ca(V)3 T-type calcium channels remains poorly characterized compared with high voltage-activated Ca(V)1 and Ca(V)2 calcium channels. Notably, it is yet unresolved whether Ca(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(V)3.1, Ca(V)3.2, and Ca(V)3.3 currents in various mammalian cell lines. Notably, we show that protein kinase effects occur at physiological temperature ( approximately 30-37 degrees C) but not at room temperature ( approximately 22-27 degrees 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(V)2.3 currents. We also report that neither Ca(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(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(V)3 T-channels and further highlight the key role of the physiological temperature in the effects described.
Insights
Protein kinase A (PKA) and protein kinase C (PKC) significantly enhance Ca(V)3 T-type calcium channel activity in mammalian cells. These kinase effects on T-channels are temperature-dependent, occurring at physiological temperatures but not at room temperature.
Area of Science:
- Molecular and Cellular Biology
- Neuroscience
- Ion Channel Physiology
Background:
- Low voltage-activated Ca(V)3 T-type calcium channels are less understood than Ca(V)1 and Ca(V)2 channels.
- The role of protein kinases in modulating Ca(V)3 channel function in mammals is largely unknown.
Purpose of the Study:
- To investigate whether protein kinases modulate Ca(V)3 T-type calcium channels in mammalian cells.
- To characterize the conditions, including temperature, under which kinase modulation occurs.
Main Methods:
- Electrophysiological recordings in various mammalian cell lines to measure Ca(V)3 currents.
- Activation of protein kinase A (PKA) and protein kinase C (PKC) using specific activators.
- In vitro phosphorylation assays to assess direct interaction between PKA and Ca(V)3.2 channels.
Main Results:
- PKA and PKC activation significantly increased Ca(V)3.1, Ca(V)3.2, and Ca(V)3.3 currents.
- Kinase-mediated potentiation of Ca(V)3 currents was observed at physiological temperatures (30-37°C) but not at room temperature (22-27°C).
- Direct phosphorylation of Ca(V)3.2 channels by PKA was demonstrated in vitro; surface expression and macroscopic properties remained unchanged.
Conclusions:
- PKA and PKC play a significant role in modulating Ca(V)3 T-type calcium channel activity.
- Physiological temperature is a critical factor for observing kinase-mediated modulation of Ca(V)3 channels.
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