Inhibition of the type 1 inositol 1,4,5-trisphosphate-sensitive Ca2+ channel by calmodulin antagonists

Khan, Shahla Zafar; Dyer, Jeanette L.; Michelangeli, Francesco

doi:10.1016/s0898-6568(00)00140-6

Cited by 22 publications

(15 citation statements)

References 28 publications

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“…This approach, however, resulted in different observations and led to some confusion. W-7, calmidazolium, trifluoperazine, chlorpromazine, and fendiline caused Ca 2ϩ release from the endoplasmic reticulum (33)(34)(35), whereas it was also reported that they directly inhibited IICR without interacting with CaM (36).…”

Section: Remains Unclear Exogenous Cam Inhibits Iicr In a Camentioning

confidence: 99%

Endogenously Bound Calmodulin Is Essential for the Function of the Inositol 1,4,5-Trisphosphate Receptor

Kasri

Török

Galione

et al. 2006

Journal of Biological Chemistry

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Calmodulin (CaM) is a ubiquitous Ca2؉ sensor protein that plays an important role in regulating a large number of Ca 2؉ channels, including the inositol 1,4,5-trisphosphate receptor (IP 3 R). Despite many efforts, the exact mechanism by which CaM regulates the IP 3 R still remains elusive. Here we show, using unidirectional 45 (17). This can be explained by the large conformational change that the IP 3 R undergoes in the presence of Ca 2ϩ and which may be necessary for CaM action. This interaction may provide a tonic regulation of IP 3 R activity and can explain the low sensitivity of the IP 3 R in neuronal tissues where CaM is highly expressed. The role of the Ca 2ϩ -dependent CaM-binding site in the regulatory domain, however, still remains to be elucidated.CaM-binding sites have not merely been identified as regulatory sites but have also recently been implicated in inter-and intrasubunit interactions. For example, the CaM-binding domain of the RyR1 modulates channel activity by at least two mechanisms: 1) by direct binding of CaM and 2) by forming a bridge between two different regions on the RyR1. Peptides of the RyR1 were used to demonstrate that the CaM-binding region is indeed directly involved in intersubunit interactions between the RyR subunits (18). In the case of small conductance K ϩ channels, CaM is involved in intersubunit interactions. Functional small conductance K ϩ channels are heteromeric complexes with CaM, which is constitutively associated with the ␣-subunits in a Ca 2ϩ -independent manner (19). In this study, we investigated whether endogenously bound CaM is essential for IP 3 R functioning. To test this hypothesis, we measured IP 3 R activity in the presence of different synthetic peptides corresponding to the CaM-binding region of myosin light-chain kinase (MLCK), which has a very high affinity for CaM, and in the presence of peptides corresponding to CaM-binding sites of the IP 3 R and other

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Section: Remains Unclear Exogenous Cam Inhibits Iicr In a Camentioning

confidence: 99%

Endogenously Bound Calmodulin Is Essential for the Function of the Inositol 1,4,5-Trisphosphate Receptor

Kasri

Török

Galione

et al. 2006

Journal of Biological Chemistry

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“…In some cases, CaM antagonists have been reported to interact directly with and to inhibit cation channel activity independently of CaM. For instance, TFP and calmidazolium chloride inhibit the extent of Ca 2þ release from type 1 inositol triphosphate receptor channels (Khan et al, 2001). In plants, Gilroy and colleagues (1987) reported that CaM antagonists induced a slow and steady increase in cytosolic Ca 2þ in carrot protoplasts.…”

Section: Introductionmentioning

confidence: 99%

Rapid Transcriptome Changes Induced by Cytosolic Ca2+ Transients Reveal ABRE-Related Sequences as Ca2+-Responsive cis Elements in Arabidopsis

et al. 2006

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The regulation of gene expression by cellular calcium is crucial for plant defense against biotic and abiotic stresses. However, the number of genes known to respond to specific transient calcium signals is limited, and as yet there is no definition of a calcium-responsive cis element in plants. Here, we generated specific cytosolic calcium transients in intact Arabidopsis thaliana seedlings and linked them to early transcriptome changes, followed by bioinformatic analysis of the responsive genes. A cytosolic calcium transient induced by calmodulin antagonists and blocked by lanthanides was characterized using aequorin-based luminometry and photon imaging. Analysis of transcriptome changes revealed 230 calcium-responsive genes, of which 162 were upregulated and 68 were downregulated. These include known early stress-responsive genes as well as genes of unknown function. Analysis of their upstream regions revealed, exclusively in the upregulated genes, a highly significant occurrence of a consensus sequence (P < 10−13) comprising two abscisic acid–specific cis elements: the abscisic acid–responsive element (ABRE; CACGTG[T/C/G]) and its coupling element ([C/A]ACGCG[T/C/A]). Finally, we show that a tetramer of the ABRE cis element is sufficient to confer transcriptional activation in response to cytosolic Ca2+ transients. Thus, at least for some specific Ca2+ transients and motif combinations, ABREs function as Ca2+-responsive cis elements.

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“…It was shown to cause inhibition of phospholipase A2 and calmodulin (43,44). Both phospholipase A2 and calmodulin could potentially be implicated in ROS production.…”

Section: Accumulation Of Ros Triggers Necrosis Of H9c2mentioning

confidence: 99%

“…In our experiments, TFP caused 2-fold protection of cells from necrosis induced by transient energy deprivation. TFP was reported to inhibit calmodulin (43), but the calmodulin-inhibiting activity of TFP appears to be unrelated to cell protection for two reasons. First, necrosis of H9c2 was not inhibited by depletion of Ca 2ϩ (data not shown).…”

mentioning

confidence: 99%

Regulation of Necrosis of H9c2 Myogenic Cells upon Transient Energy Deprivation

Yaglom

Ekhterae

Gabai

et al. 2003

Journal of Biological Chemistry

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Subjecting myogenic H9c2 cells to transient energy deprivation leads to a caspase-independent death with typical features of necrosis. Here we show that the rupture of cytoplasmic membrane, the terminal event in necrosis, is shortly preceded by rapid depolarization of mitochondrial membranes. The rapid deenergization of mitochondria critically depended upon prior generation of reactive oxygen species (ROS) during ATP depletion stage. Accordingly, expression of catalase prevented mitochondrial depolarization and averted subsequent necrosis. Interestingly, trifluoperazine, a compound that protects cells from ischemic insults, prevented necrosis of H9c2 cells through inhibition of ROS production. Other factors that regulated the mitochondrial membrane depolarization and subsequent loss of plasma membrane integrity include a stress kinase JNK activated at early steps of recovery from ATP depletion, as well as an apoptotic inhibitory protein ARC. Accordingly, inhibition of JNK or overexpression of ARC prevented mitochondrial depolarization and rescued H9c2 cells from necrosis. ROS and JNK affected mitochondrial deenergization and necrosis independently of each other since inhibition of ROS production did not prevent activation of JNK, whereas inhibition of JNK did not suppress ROS accumulation. Therefore, JNK activation and ROS production represent two independent pathways that control mitochondrial depolarization and subsequent necrosis of cells subjected to transient energy deprivation. Overexpression of ARC, although preventing mitochondrial depolarization, did not affect either JNK activation or production of ROS. The major heat shock protein Hsp72 inhibited JNK-related steps of necrotic pathway but did not affect ROS accumulation. Interestingly, mitochondrial depolarization and subsequent necrosis can be suppressed by an Hsp72 mutant Hsp72⌬EEVD, which lacks chaperone function but can efficiently suppress JNK activation. Thus, Hsp72 is directly implicated in a signaling pathway, which leads to necrotic death.

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Inhibition of the type 1 inositol 1,4,5-trisphosphate-sensitive Ca2+ channel by calmodulin antagonists

Cited by 22 publications

References 28 publications

Endogenously Bound Calmodulin Is Essential for the Function of the Inositol 1,4,5-Trisphosphate Receptor

Endogenously Bound Calmodulin Is Essential for the Function of the Inositol 1,4,5-Trisphosphate Receptor

Rapid Transcriptome Changes Induced by Cytosolic Ca2+ Transients Reveal ABRE-Related Sequences as Ca2+-Responsive cis Elements in Arabidopsis

Regulation of Necrosis of H9c2 Myogenic Cells upon Transient Energy Deprivation

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