AUTHOR=Gomis-Perez Carolina , Soldovieri Maria V. , Malo Covadonga , Ambrosino Paolo , Taglialatela Maurizio , Areso Pilar , Villarroel Alvaro TITLE=Differential Regulation of PI(4,5)P2 Sensitivity of Kv7.2 and Kv7.3 Channels by Calmodulin JOURNAL=Frontiers in Molecular Neuroscience VOLUME=10 YEAR=2017 URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2017.00117 DOI=10.3389/fnmol.2017.00117 ISSN=1662-5099 ABSTRACT=
- Calmodulin-dependent Kv7.2 current density without the need of binding calcium. - Kv7.2 current density increase is accompanied with resistance to PI(4,5)P2 depletion. - Kv7.3 current density is insensitive to calmodulin elevation. - Kv7.3 is more sensitive to PI(4,5)P2 depletion in the presence of calmodulin. - Apo-calmodulin influences PI(4,5)P2 dependence in a subunit specific manner.
The identification and understanding of critical factors regulating M-current functional density, whose main components are Kv7.2 and Kv7.3 subunits, has profound pathophysiological impact given the important role of the M-current in neuronal excitability control. We report the increase in current density of Kv7.2 channels by calmodulin (CaM) and by a mutant CaM unable to bind Ca2+ (CaM1234) revealing that this potentiation is calcium independent. Furthermore, after co-expressing a CaM binding protein (CaM sponge) to reduce CaM cellular availability, Kv7.2 current density was reduced. Current inhibition after transient depletion of the essential Kv7 co-factor phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) by activating