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

Abstract.

The effects of a lipid component of oxidized low-density lipoproteins (ox-LDL), l-α-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 µM) 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 (E _r) 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. E _r 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 µM). Shifts in E _r 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.