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-L DL), L-alpha-palmitoyl lysophosphatidylcholine (LPC), on membrane currents of isolated canine renal artery smooth muscle cells (RASMC) were examined u sing the whole-cell configuration of the patch-clamp technique. In RASMC ex posed to nominally Ca2+-free solutions and dialyzed with 0.1 mM EGTA and 14 0 mM K+, superfusion with LPC (10 mu M) elicited spontaneous transient outw ard currents (STOCs) and/or spontaneous transient inward currents (STICs), followed by the activation of a large voltage-independent current with a re versal potential (E-r) close to 0 mV. Buffering intracellular Ca2+ with 10 mM BAPTA prevented the appearance of STOCs and STICs, but not the activatio n of the voltage-independent current. E-r of the LPC-induced voltage-indepe ndent 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 bloc ked by gadolinium (Gd3+; 10 mu M). Shifts in E-r of the LPC-induced I-NSC i n 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 app earance 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 relaxa tion.