Following stimulation with lysophosphatidylcholine (LPC), nonselective cation channels were activated in cultured brain macrophages. LPC-activated non-selective cation channels were permeable for monovalent and divalent cations (Cs+>K+>Na+>NMG+>Ca2+), but were impermeable for chloride or other anions. Non-selective cation currents exhibited neither time- nor voltage-dependent activation and inactivation. Currents were abolished by Gd3+, La3+, Zn2+ and G. spatulata venom, but were unaffected by diltiazem, LOE908MS, amiloride and DIDS. Ca2+ influx through non-selective cation channels caused sustained increases in the intracellular Ca2+ concentration and subsequent activation of Ca2+-activated K+ channels. LPC-induced Ca2+-activated K+ currents of macrophages were inhibited by charybdotoxin and clotriomazole, but were unaffected by apamin and paxilline. LPC caused the release of interleukin-1 by an ATP receptor-independent mechanism. This LPC-stimulated cytokine release was dependent on Ca2+ influx through non-selective cation channels and on membrane hyperpolarization induced by the activity of Ca2+-activated K+ channels.

Supported by DFG grants SFB 507/C7 and Schw 407/9-1,2.