Lysophosphatidic acid stimulates two ion currents in cultured human retinal pigment epithelial cells

Lysophosphatidic acid (LPA) is a simple phospholipid that can be released from thrombin-activated platelets and growth factor-activated fibroblasts. The effects of this lipid signaling molecule on membrane currents of cultured human retinal pigment epithelial (RPE) cells were investigated using whole cell recording techniques. Bath application of LPA evoked an inward current that was sometimes preceded by an outward current. The inward current reversed near 0 mV regardless of Cl^- equilibrium potential and was suppressed by lowering extracellular [Na⁺] or application of Cd²⁺ (3 mM) suggesting that it is a non-selective cation current. The outward current reversed near the K⁺ equilibrium potential (E(K)) suggesting it is carried predominantly by K⁺ ions. The effects of LPA appear to be mediated by a receptor rather than non-specific detergent effects since: (a) both currents showed a similar saturating concentration/response relationship: (b) lysophosphatidylcholine, which has the same lipid tail as LPA, was significantly less effective than LPA in evoking inward currents: (c) LPA-evoked currents diminished with repeated applications of LPA suggesting receptor desensitization or washout of second messenger systems during whole cell recording: and (d) pertussis and cholera toxin pre- treatment suppressed the inward current, although not the outward current. Bath application of a calcium ionophore, ionomycin, stimulated an outward current which, like the LPA-sensitive current, reversed near E(K). The results suggest that LPA stimulates one or more receptor subtypes which can associate with both a pertussis toxin-sensitive G protein resulting in generation of an inward cation current and a pertussis toxininsensitive G protein resulting in generation of an outward current carried predominantly by K⁺.