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.