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The lipid connection–regulation of voltage-gated Ca2+ channels by phosphoinositides

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Abstract

Recent findings have revealed a pivotal role for phospholipids phosphatidylinositol -4,5-biphosphate (PIP2) and phosphatidylinositol -3,4,5-trisphosphate (PIP3) in the regulation of high voltage-activated (HVA) Ca2+ channels. PIP2 exerts two opposing actions on HVA Ca2+ channels: It stabilizes their activity but also produces a voltage-dependent inhibition that can be antagonized by protein kinase A (PKA) phosphorylation. PIP2 depletion and arachidonic acid together mediate the slow, voltage-independent inhibition of HVA Ca2+ channels by G q/11 -coupled receptors in neurons. A sufficient level of plasma membrane PIP2 also appears to be necessary for G βγ -mediated inhibition. On the other hand, increased production of PIP3 by PI-3 kinases promotes trafficking of HVA Ca2+ channels to the plasma membrane. This review discusses these findings and their implications.

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Authors and Affiliations

  1. Department of Biological Sciences, Columbia University, New York, NY, 10027, USA

    Ioannis E. Michailidis, Yun Zhang & Jian Yang

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  1. Ioannis E. Michailidis
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  2. Yun Zhang
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Correspondence to Jian Yang.

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Michailidis, I.E., Zhang, Y. & Yang, J. The lipid connection–regulation of voltage-gated Ca2+ channels by phosphoinositides. Pflugers Arch - Eur J Physiol 455, 147–155 (2007). https://doi.org/10.1007/s00424-007-0272-9

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  • DOI: https://doi.org/10.1007/s00424-007-0272-9

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