Lysophosphatidylcholine triggers intracellular calcium release and activation of non-selective cation channels in renal arterial smooth muscle cells.

The effects of a lipid component of oxidized low-density lipoproteins (ox-LDL), L-alpha-palmitoyl-lysophosphatidylcholine (LPC), on membrane currents of isolated canine renal artery smooth muscle cells (RASMC) were examined using the whole-cell configuration of the patch-clamp technique. In RASMC exposed to nominally Ca2+-free solutions and dialyzed with 0.1 mM EGTA and 140 mM K+, superfusion with LPC (10 microM) elicited spontaneous transient outward currents (STOCs) and/or spontaneous transient inward currents (STICs), followed by the activation of a large voltage-independent current with a reversal potential (Er) close to 0 mV. Buffering intracellular Ca2+ with 10 mM BAPTA prevented the appearance of STOCs and STICs, but not the activation of the voltage-independent current. Er of the LPC-induced voltage-independent current exhibited sensitivity to changes in [K+]o and [Na+]o in a manner consistent with a non-selective cation current (I(NSC)) and was blocked by gadolinium (Gd3+; 10 microM). Shifts in Er of the LPC-induced I(NSC) in response to changes in [Ca2+]o were used to estimate a relative Ca2+ to Na+ permeability ratio (P(Ca)/P(Na)) of 1.67. These results suggest that LPC causes abnormal sarcoplasmic reticulum Ca2+ regulation, leading to the appearance of STOCs and STICs, and the activation of I(NSC) in vascular smooth muscle cells. These effects may explain the ability of ox-LDLs to elevate [Ca2+]i in vascular smooth muscle and inhibit endothelium-dependent relaxation.