Article date: June 1996
By: Takaaki Ikemoto, Masamitsu Lino, Makoto Endo, in Volume 118, Issue 3, pages 690-694
Calmodulin (CaM) has a biphasic effect on Ca2+‐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.
A CaM antagonist, trifluoperazine (TFP), potentiated the CICR in a dose‐dependent manner (10–300 μm) at pCa 6, where a simple reversal of the CaM effect would be inhibition of the CICR. Furthermore, 100 μm 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.
The biphasic effect of CaM on the CICR was observed even in the presence of high concentrations of CaM antagonists or CaM‐binding peptides.
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.
Calmodulin (CaM) has a biphasic effect on Ca2+‐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.
A CaM antagonist, trifluoperazine (TFP), potentiated the CICR in a dose‐dependent manner (10–300 μm) at pCa 6, where a simple reversal of the CaM effect would be inhibition of the CICR. Furthermore, 100 μm 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.
The biphasic effect of CaM on the CICR was observed even in the presence of high concentrations of CaM antagonists or CaM‐binding peptides.
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.
DOI: 10.1111/j.1476-5381.1996.tb15455.x
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