Differential Regulation of PI(4,5)P2 Sensitivity of Kv7.2 and Kv7.3 Channels by Calmodulin

Frontiers in Molecular Neuroscience
Carolina Gomis-PerezAlvaro Villarroel

Abstract

HIGHLIGHTS - 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 Ca(2+) (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 Danio rerio voltage sensitive phosphatase (DrVSP) was blunted by co-expressing CaM1234 or the CaM sponge. In addi...Continue Reading

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Citations

Jul 20, 2018·Biomolecules·Alessandro Alaimo, Alvaro Villarroel
Jul 13, 2019·International Journal of Molecular Sciences·Maria Virginia SoldovieriMaurizio Taglialatela
Feb 23, 2020·International Journal of Molecular Sciences·Eider NúñezAlvaro Villarroel
Jan 24, 2019·International Journal of Molecular Sciences·Janire UrrutiaAlvaro Villarroel
Feb 9, 2021·Frontiers in Physiology·Wenhui Zhuang, Zhiqiang Yan
Jun 22, 2021·Frontiers in Molecular Neuroscience·Deepanjali Dwivedi, Upinder S Bhalla

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Methods Mentioned

BETA
transfection

Software Mentioned

Excel
pCLAMP
SigmaPlot

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