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

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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