Phospholipid headgroup superlattice modulation of cardiac calcium channel activity
Cannon, Brian L.
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The plasma membrane of cells consists of phospholipids, sterols, and proteins and maintains a steady composition through a regulatory mechanism that remains largely unknown. The interactions that occur among the membrane constituents are complex and are involved in compositional control. Among the proteins embedded is a class of transmembrane proteins called ion channels, specifically, the ryanodine receptors located in the sarcoplasmic reticulum of myocytes. These channels are responsible for the release of Ca ions, necessary for the activation of myofilaments to produce contractions. The receptors, through a process known as gating, undergo changes in conformation during the transition between open and closed states. Since proteins are surrounded by lipids and change conformations, the lipid-protein interactions must influence the protein state by hydrophobic coupling or on the headgroup level. By reconstituting the channels in planar lipid bilayers composed of two phospholipids with differing headgroup sizes, POPE and POPC and varying the ratio of the two lipids that form the bilayer, the channel functioned as sensors to determine how bilayer changes affect the channel. A peak in channel activity was observed over a narrow region of high PE:PC bilayers, indicating that lipid-protein interactions do have an important role in channel function. The results are interpreted as reflecting lateral organization by the lipids on the headgroup level in order to minimize the stress across the bilayer due to deformation, curvature, and packing, providing a favorable condition for the channel to enter its preferred conformation.