Membrane-localized β-subunits alter the PIP2 regulation of high-voltage activated Ca2+ channels

摘要: The β-subunits of voltage-gated Ca2+ (CaV) channels regulate the functional expression and several biophysical properties high-voltage–activated CaV channels. We find that also determine channel regulation by membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2). When CaV1.3, -2.1, or -2.2 are cotransfected with β3-subunit, a cytosolic protein, they can be inhibited activating voltage-sensitive lipid phosphatase to deplete PIP2. these coexpressed β2a-subunit, palmitoylated peripheral inhibition is much smaller. PIP2 sensitivity could increased disabling two palmitoylation sites in β2a-subunit. To further test effects targeting on regulation, N terminus Lyn was ligated onto β3-subunit confer lipidation. This chimera, like displayed plasma localization, slowed inactivation CaV2.2 channels, current density. In addition, Lyn-β3 subunit significantly decreased depletion. Evidently lipidation anchoring compete Compared β3-subunits alone, depletion attenuated when β2a β3. Our data suggest currents neurons would regulated degree depends their endogenous β-subunit combinations.