NONSPECIFIC EFFECTS OF CALCIUM-ENTRY ANTAGONISTS IN MAST-CELLS

Calcium entry in non-excitable cells occurs through calcium-selective currents activated secondarily to store depletion and/or through non-s elective cation channels (e. g., receptor- or second-messenger-activat ed channels). The driving force for calcium influx can be modified by chloride or potassium channels, which set the membrane potential of ce lls. Together, these conductances determine the extent of calcium entr y. Mast cells are an excellent model system for studying calcium influ x, because calcium-release-activated calcium currents (I-CRAC), second -messenger-activated non-selective currents and chloride currents are present in these cells. Whole-cell patch-clamp recordings were used to test the effects of the commonly used calcium entry blockers econazol e and SK&F 96365, as well as the antiallergic and anti-inflammatory dr ugs tenidap, ketotifen and cromolyn on these channels. All tested drug s blocked the three different channel types with a similar order of ma gnitude (IC50 values ranging from micromolar to millimolar). Hence, th ese drugs cannot be used to discriminate between different calcium ent ry mechanisms.