Lysophospholipids modulate voltage-gated calcium channel currents in pituitary cells; effects of lipid stress.

Voltage-gated calcium channels (VGCCs) are osmosensitive. The hypothesis that this property of VGCCs stems from their susceptibility to alterations in the mechanical properties of the bilayer was tested on VGCCs in pituitary cells using cone-shaped lysophospholipids (LPLs) to perturb bilayer lipid stress. LPLs of different head group size and charge were used: lysophosphatidylcholine (LPC), lysophosphatidylinositol (LPI), lysophosphatidylserine (LPS) and lysophosphatidylethanolamine (LPE). Phosphatidylcholine (PC) and LPC (C6:0) were used as controls. We show that partition of both LPC and LPI into the membrane of pituitary cells suppressed L-type calcium channel currents (I(L)). This suppression of I(L) was slow in onset, reversible upon washout with BSA and associated with a depolarizing shift in activation ( approximately 8mV). In contrast to these effects of LPC and LPI on I(L), LPS, LPE, PC and LPC (C6:0) exerted minimal or insignificant effects. This difference may be attributed to the prominent conical shape of LPC and LPI compared to the shapes of LPS and LPE (which have smaller headgroups), and to PC (which is cylindrical). The similar effects of LPC and LPI on I(L), despite differences in the structure and charge of their headgroups suggest a common lipid stress dependent mechanism in their action on VGCCs.