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

Published Date
June 2010, Vol.47(6):514–524, doi:10.1016/j.ceca.2010.04.006

Author 

Galia Ben-Zeev

Michael Telias

Itzhak Nussinovitch ^,

Department of Medical Neurobiology, Institute for Medical Research-Israel-Canada, the Hebrew University Faculty of Medicine, Jerusalem, Israel

Received 9 December 2009. Revised 28 April 2010. Accepted 28 April 2010. Available online 26 May 2010. 

Abstract

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 (∼8 mV). 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.

Keywords

Lysophosphatidylcholine

Lysophostatidylinisitol

Ca²⁺ channels

L-type Ca²⁺channels

T-type Ca²⁺ channels

Lipid bilayer

Osmosensitivity

Mechanosensitivity

Pituitary cells

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  Corresponding author at: Department of Medical Neurobiology, Institute for Medical Research-Israel-Canada, The Hebrew University Faculty of Medicine, P.O.B. 12272, Jerusalem 91120, Israel. Tel.: +972 2 6757449; fax: +972 2 6757451.

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