The lipid connection-regulation of voltage-gated Ca(2+) channels by phosphoinositides.
Recent findings have revealed a pivotal role for phospholipids phosphatidylinositol -4,5-biphosphate (PIP(2)) and phosphatidylinositol -3,4,5-trisphosphate (PIP(3)) in the regulation of high voltage-activated (HVA) Ca(2+) channels. PIP(2) exerts two opposing actions on HVA Ca(2+) channels: It stabilizes their activity but also produces a voltage-dependent inhibition that can be antagonized by protein kinase A (PKA) phosphorylation. PIP(2) depletion and arachidonic acid together mediate the slow, voltage-independent inhibition of HVA Ca(2+) channels by G( q/11 )-coupled receptors in neurons. A sufficient level of plasma membrane PIP(2) also appears to be necessary for G( betagamma )-mediated inhibition. On the other hand, increased production of PIP(3) by PI-3 kinases promotes trafficking of HVA Ca(2+) channels to the plasma membrane. This review discusses these findings and their implications.
Michailidis
Ioannis E
IE
Department of Biological Sciences, Columbia University, New York, NY, 10027, USA.
Zhang
Yun
Y
Yang
Jian
J
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D008055:Lipids / Q000737:chemistry / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000494:pharmacology*; D015290:Second Messenger Systems / Q000187:drug effects
D015220:Calcium Channels; D008055:Lipids; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D016718:Arachidonic Acid; D019869:Phosphatidylinositol 3-Kinases