Increases in intracellular Ca2+ concentration ([Ca2+]i) after addition of the carboxylic Ca(2+)-transporting ionophore ionomycin have been reported to be inhibited by depolarization in mouse T- and B-lymphocytes, a result attributed to effects on the plasma-membrane Ca2+ pump. The present experiments were undertaken to test the hypothesis that activation of electrogenic Ca2+ uptake, due to release of Ca2+i from intracellular pools, underlies the membrane-potential (Em)-sensitivity of ionomycin-mediated Ca2+ uptake in T-lymphocytes. To address this proposal we have compared the characteristics of Ca2+ influx induced by ionomycin with those of Ca2+ influx activated by release of Ca2+ from intracellular stores (store-regulated Ca2+ uptake, SRCU). The endosomal Ca(2+)-ATPase inhibitor thapsigargin was used to bring about loss of Ca2+ from intracellular pools. In support of this hypothesis, we report that: (1) ionomycin releases Ca2+ from a thapsigargin-sensitive endosomal pool, a pool previously demonstrated to regulate electrogenic SRCU in rat thymic lymphocytes, (2) Ca2+ and Mn2+ uptake mediated by low doses of ionomycin are inhibited by compounds previously reported to inhibit SRCU, and (3) in the absence of SRCU, ionomycin-mediated Ca2+ uptake displays no sensitivity to Em. We conclude that activation of electrogenic SRCU can adequately account for the Em-sensitivity of Ca2+ flux previously attributed to alterations in Ca(2+)-pump activity. Such a mechanism of action may underlie previous reports of electrogenic Ca2+ transport mediated by ionomycin in other tissues.
Research Article|November 15 1993
Ionomycin activates electrogenic Ca2+ influx in rat thymic lymphocytes
M J Mason;
Biochem J (1993) 296 (1): 33-39.
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M J Mason, S Grinstein; Ionomycin activates electrogenic Ca2+ influx in rat thymic lymphocytes. Biochem J 15 November 1993; 296 (1): 33–39. doi: https://doi.org/10.1042/bj2960033
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