1997
DOI: 10.1042/bj3250177
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Effects of thimerosal on the transient kinetics of inositol 1,4,5-trisphosphate-induced Ca2+ release from cerebellar microsomes

Abstract: Thimerosal, a thiol-reactive reagent, has been shown to increase the cytosolic Ca# + concentration in a variety of cells by sensitizing inositol 1,4,5-trisphosphate (InsP $ ) receptors. Thimerosal can have both sensitizing (at concentrations of 2 µM) and inhibitory (at concentrations of 2 µM) effects on InsP $ -induced Ca# + release (IICR) from cerebellar microsomes. Transient kinetic studies were performed by employing a fluorimetric stopped-flow approach using fluo-3. IICR was found to be a biexponential pro… Show more

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Cited by 21 publications
(7 citation statements)
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“…Functional effects of thimerosal were reported previously for DT40 cells expressing IP 3 R1 or IP 3 R3 [29], but use of the same single sub-threshold concentration of IP 3 for both IP 3 R subtypes when IP 3 R3 is much less sensitive to IP 3 (Figure 1 and Table 1) [35] compromised the conclusion that thimerosal sensitizes only IP 3 R1. Our results, demonstrating that low concentrations of thimerosal sensitize IP 3 R1 and IP 3 R2 to IP 3 while inhibiting IP 3 R3, are consistent with previous studies in which thimerosal [29,36–42] or other thiol reagents [40,43,44] potentiated IP 3 -evoked Ca 2+ signals in cells expressing predominantly IP 3 R1 [29,37,42] or IP 3 R2 [38,40,43,44], but not in cells where IP 3 R3 predominates [29,39,41]. We conclude that within homotetrameric populations of IP 3 R, thimerosal potentiates responses from IP 3 R1 and IP 3 R2, but inhibits IP 3 R3.…”
Section: Resultssupporting
confidence: 93%
“…Functional effects of thimerosal were reported previously for DT40 cells expressing IP 3 R1 or IP 3 R3 [29], but use of the same single sub-threshold concentration of IP 3 for both IP 3 R subtypes when IP 3 R3 is much less sensitive to IP 3 (Figure 1 and Table 1) [35] compromised the conclusion that thimerosal sensitizes only IP 3 R1. Our results, demonstrating that low concentrations of thimerosal sensitize IP 3 R1 and IP 3 R2 to IP 3 while inhibiting IP 3 R3, are consistent with previous studies in which thimerosal [29,36–42] or other thiol reagents [40,43,44] potentiated IP 3 -evoked Ca 2+ signals in cells expressing predominantly IP 3 R1 [29,37,42] or IP 3 R2 [38,40,43,44], but not in cells where IP 3 R3 predominates [29,39,41]. We conclude that within homotetrameric populations of IP 3 R, thimerosal potentiates responses from IP 3 R1 and IP 3 R2, but inhibits IP 3 R3.…”
Section: Resultssupporting
confidence: 93%
“…Whether this has direct relevance to our finding that DTT enhanced the inhibitory effects of TPEN is unclear. Nevertheless, both InsP $ and ryanodine receptor Ca# + channels are present in mouse eggs, and they are known to possess critical thiol groups that are involved in effecting Ca# + release [1,29,33]. It is possible that endogenous heavy-metal ions associated with these thiol groups can modulate Ca# + release in mouse eggs.…”
Section: Discussionmentioning
confidence: 99%
“…In accordance with this, steep curves for dose-dependent flux inhibition by cytosolic Ca# + have been obtained at high InsP $ concentrations in the cerebellum [17][18][19]. However, the co-operativity of IICR in the cerebellum remains controversial [52] and we cannot exclude the possibility that Ca# + inhibits InsP $ R activity via a mechanism other than the decrease of InsP $ binding, by directly affecting channel activity. Nevertheless, to be effective, such a mechanism might require the conversion of InsP $ R to the lower-affinity state described here.…”
Section: [$H]inspmentioning
confidence: 68%