Low concentrations of caffeine raise intracellular calcium concentration only in the presence of extracellular calcium in cultured molluscan neurons

1. The effects of low concentrations of caffeine (100 and 300 mu M) on the intracellular calcium concentration [Ca2+](i) in four cultured, identified neurons of the pond snail Lymnaea stagnalis (L) were investigated. 2. Intracellular CA(2+) levels in these neurons were measured with the cell-permeable Ca2+ indicator Fura-2/AM, both in the presence and absence of extracellular Ca-2 (O-Ca2+/EGTA). 3. In the presence of Ca2+ in the external medium, caffeine was found to induce a substantial elevation in the free [Ca2+](i) in all cell types. 4. In some cases, the rise in [Ca2+](i) was found to be both time- and concentration dependent. 5. Low doses of caffeine did not produce any appreciable rise in [Ca2+](i) in the absence of Ca2+ in the external medium, but calcium was still available from stores, as clinical concentrations of halothane rose [Ca2+](i) in the absence of extracellular calcium. 6. These results indicate that the actions of caffeine, when applied at low concentrations, are dependent on extracellular calcium. Copyright (C) 1997 Elsevier Science Inc.