Effects of low density lipoprotein on cytosolic [Ca++] in cultured rat mesangial cells

BACKGROUND: Recently, a low density lipoprotein (LDL) receptor has been identified in mesangial cells. However, the nature of intracellular signals in mesangial cells after exposure to LDL is unclear. METHODS: We studied the effect of LDL on cultured rat mesangial cell [Ca++]i using spectrofluorometry. RESULTS: Addition of LDL (15 micrograms/mL) produced a rapid, transient, and dose-dependent rise in [Ca++]i within seconds, returning to baseline in 6 minutes. No further rise was observed at higher LDL concentrations. No significant rise in [Ca++]i was observed with LDL in cells placed in a Ca(++)-free medium. The [Ca++]i rise was greatly attenuated in magnitude and duration when lanthanum was used. In contrast, verapamil failed to block the LDL-induced rise in [Ca++]i. Addition of LDL did not alter production of inositol 1,4,5-triphosphate (IP3) by mesangial cells. CONCLUSIONS: Low density lipoprotein caused a transient rise in [Ca++]i in cultured rat mesangial cells. The observed rise in [Ca++]i was largely caused by influx of extracellular Ca++ through receptor-gated channels. Mobilization from intracellular stores and activation of IP3 were not involved. The rise in [Ca++]i may mediate the effects of LDL on mesangial cell function.