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. 1996 Jun;118(3):690–694. doi: 10.1111/j.1476-5381.1996.tb15455.x

Effect of calmodulin antagonists on calmodulin-induced biphasic modulation of Ca(2+)-induced Ca2+ release.

T Ikemoto 1, M Iino 1, M Endo 1
PMCID: PMC1909698  PMID: 8762095

Abstract

1. Calmodulin (CaM) has a biphasic effect on Ca(2+)-induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR): potentiation and inhibition at low (pCa > 6.0) and high (pCa 5) Ca2+ concentrations, respectively. To characterize the mode of action of CaM, we studied the effect of CaM antagonists on the CICR in skinned muscle fibres of the rabbit. Ca2+ release was measured by microfluorometry with Fura-2. 2. A CaM antagonist, trifluoperazine (TFP), potentiated the CICR in a dose-dependent manner (10-300 microM) at pCa 6, where a simple reversal of the CaM effect would be inhibition of the CICR. Furthermore, 100 microM TFP sensitized the CICR to Ca2+. A similar effect was produced by other CaM antagonists that were tested: chlorpromazine, W-7, mastoparan, and peptide fragment of CaM-binding residues of CaM-dependent protein kinase II. 3. The biphasic effect of CaM on the CICR was observed even in the presence of high concentrations of CaM antagonists or CaM-bindings peptides. 4. From these results we suggest that CaM has a unique mode of action on the CICR which is quite different from the effect of CaM on known enzymes.

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Selected References

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