Lithium opens store-operated channels in human platelets.
Ca(2+) release from internal stores as a result of activation of phospholipase C or inhibition of the endoplasmic reticulum pump is accompanied by Ca(2+) influx from the extracellular space. Measurement of intracellular calcium concentration and fluorescence quenching in Fura2-loaded cells showed that platelets preincubated in lithium have significantly higher basal, but lower agonist-stimulated influx of Mn(2+) (acting as a surrogate of Ca(2+) influx), than platelets reloaded with calcium in a normal sodium medium. There is no difference in the basal entry of divalent ion in platelets preincubated in sodium, lithium, or N-methyl glucamine in the absence of calcium. In platelets preincubated in lithium there is a higher basal Mn(2+) entry without further increase upon store depletion by thapsigargin. In contrast, a significant increase in the divalent ion influx was found in sodium or N-methyl glucamine attributable to the opening of channels sensitive to store depletion. In the absence of extracellular calcium, the empty store opens channels and Li(+) did not have additional effect on channels that are already open. The refilling of the stores with Ca(2+) suppresses Mn(2+) entry after sodium or NMG preincubation, but not after lithium preincubation. We propose that lithium induces a calcium influx throughout store-operated channels. This hypothesis may explain the lack of additivity, in cell preincubated in lithium, of basal entry and thapsigargin-triggered entry of calcium.
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Centro de Investigaciones Cardiovasculares, Universidad Nacional de La Plata, 60 Y 120, La Plata, 1900, Argentina. Cicme@atlas.med.unlp.edu.ar
D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D020013:Calcium Signaling / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects; D008094:Lithium / Q000494:pharmacology*; D008345:Manganese / Q000097:blood; D008536:Meglumine / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D007473:Ion Channels; D008345:Manganese; D019284:Thapsigargin; D008536:Meglumine; D008094:Lithium; D012964:Sodium; D013917:Thrombin; D002118:Calcium