The Ca2+/calmodulin system in neuronal hyperexcitability

Solà, Carme; Barrón, Sonia; Tusell, Josep Maria; Serratosa, Joan

doi:10.1016/s1357-2725(01)00030-9

Cited by 47 publications

(40 citation statements)

References 69 publications

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“…This conclusion is supported by our results showing a complete inhibition of Nur77 induction by the Ca 2ϩ chelator, BAPTA, as well as the ability of two calcium ionophores to induce nur77 expression as efficiently as PGF 2␣ . CaM is a Ca 2ϩ -binding protein present in all eucaryotic cells, which is known to mediate Ca 2ϩ effects (40). The ability of the CaM inhibitor, W7, to prevent induction of the nur77 gene by PGF 2␣ indicates the participation of this protein in the PGF 2␣ signaling pathway in luteal cells.…”

Section: Discussionmentioning

confidence: 99%

A Calcium/Calmodulin-dependent Activation of ERK1/2 Mediates JunD Phosphorylation and Induction of nur77 and20α-hsd Genes by Prostaglandin F2α in Ovarian Cells

Stocco¹,

Lau²,

Gibori³

2002

Journal of Biological Chemistry

113

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We have previously demonstrated that prostaglandin F 2␣ (PGF 2␣ ) induces a rapid and transient expression of Nur77 in luteal cells. We have shown that Nur77 plays an important role in ovarian physiology by mediating the PGF 2␣ induction of 20␣-HSD, a steroidogenic enzyme involved in the catabolism of progesterone. In this report we established, using luteinized granulosa cells, that PGF 2␣ stimulates in vitro nur77 expression in a time-and dose-dependent manner. Serial 5-deletion of the nur77 promoter revealed that the necessary and sufficient elements for PGF 2␣ induction of Nur77 promoter activity are located between the nucleotides ؊86 and ؊33 upstream of the transcription start site, this region containing two AP1 elements. JunD binds to these AP1 sites, but its binding is not stimulated by PGF 2␣ . However, mutation of the AP1 sites as well as a dominant-negative JunD abolished nur77 induction by PGF 2␣ . PGF 2␣ induces phosphorylation of JunD bound to the nur77 promoter. Stimulation of nur77 expression and JunD phosphorylation were prevented by inhibitors of calcium, calmodulin, or ERK1/2 kinase. PGF 2␣ -induced ERK1/2 phosphorylation was prevented by calcium/calmodulin inhibitors. We conclude that activation of JunD through a calmodulim-dependent activation of ERK1/2 mediates nur77 induction by PGF 2␣ . Finally, we demonstrated that this molecular mechanism also mediates 20␣-hsd induction.

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Section: Discussionmentioning

confidence: 99%

A Calcium/Calmodulin-dependent Activation of ERK1/2 Mediates JunD Phosphorylation and Induction of nur77 and20α-hsd Genes by Prostaglandin F2α in Ovarian Cells

Stocco¹,

Lau²,

Gibori³

2002

Journal of Biological Chemistry

113

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“…Multiple Ca 2ϩ -dependent signaling events are based on initial binding of Ca 2ϩ to CaM, a ubiquitous eukaryotic Ca 2ϩ binding protein, followed by binding of the Ca 2ϩ /calmodulin complex to signaling enzymes such as protein kinases and phosphatases, ion channels, and other signaling molecules (for review, see Sola et al, 2001). We expressed a relatively low dose of PV from two independent transgene insertions in the LN V s of flies that were also heterozygous for a variety of CaM hypomorphic mutant alleles Figure 7.…”

Section: Camentioning

confidence: 99%

Intracellular Ca²⁺Regulates Free-Running Circadian Clock OscillationIn Vivo

Harrisingh¹,

Wu²,

Lnenicka³

et al. 2007

J. Neurosci.

125

123

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Although circadian oscillation in dynamics of intracellularbuffering in pacemaker neurons results in dose-dependent slowing of freerunning behavioral rhythms, with average period Ͼ3 h longer than control at the highest dose. The rhythmic nuclear accumulation of a transcription factor known to be essential for cellular circadian oscillation is also slowed. We also determined that Ca 2ϩ buffering interacts synergistically with genetic manipulations that interfere with either calmodulin or calmodulin-dependent protein kinase II function. These results suggest a role for intracellular Ca 2ϩ signaling in regulating intrinsic cellular oscillation in vivo.

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“…Ca 2+ influx may involve several routes, and often leads to protein phosphorylation via the Ca 2+ -activated CaM Kinase II, that makes up to 2% of all proteins in hippocampal neurons (Sola et al, 2001). Therefore, we studied the role of CaM Kinase II in the mechanisms by which seizure-like events regulated HCN channel expression.…”

Section: Seizure-like Events Regulate Hcn1 and Hcn2 Channel Expressiomentioning

confidence: 99%

“…Seizures change expression of hundreds of genes potentially through one or several key signal transduction pathways, such as those regulated by CaM Kinase II and the phosphatase calcineurin (Sola et al, 2001). Downstream from these enzymes, single transcription factors may coordinately modulate expression of receptor or channel families (Brooks-Kayal et al, 1998;Huang et al, 2002;Roberts et al, 2005).…”

Section: Seizures Orchestrate Reciprocal Changes In the Expression Ofmentioning

confidence: 99%

Mechanisms of seizure-induced ‘transcriptional channelopathy’ of hyperpolarization-activated cyclic nucleotide gated (HCN) channels

Richichi

Brewster

Bender

et al. 2008

Neurobiology of Disease

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Epilepsy may result from abnormal function of ion channels, such as those caused by genetic mutations. Recently, pathological alterations of the expression or localization of normal channels have been implicated in epilepsy generation, and termed 'acquired channelopathies'. Altered expression levels of the HCN channels--that conduct the hyperpolarization-activated current, I h --have been demonstrated in hippocampus of patients with severe temporal lobe epilepsy as well as in animal models of temporal lobe and absence epilepsies. Here we probe the mechanisms for the altered expression of HCN channels which is provoked by seizures. In organotypic hippocampal slice cultures, seizure-like events selectively reduced HCN type 1 channel expression and increased HCN2 mRNA levels, as occurs in vivo. The mechanisms for HCN1 reduction involved Ca 2+ -permeable AMPA receptors-mediated Ca 2+ influx, and subsequent activation of Ca 2+ /calmodulin-dependent protein kinase II. In contrast, upregulation of HCN2 expression was independent of these processes. The data demonstrate an orchestrated program for seizure-evoked transcriptional channelopathy involving the HCN channels, that may contribute to certain epilepsies.

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The Ca2+/calmodulin system in neuronal hyperexcitability

Cited by 47 publications

References 69 publications

A Calcium/Calmodulin-dependent Activation of ERK1/2 Mediates JunD Phosphorylation and Induction of nur77 and20α-hsd Genes by Prostaglandin F2α in Ovarian Cells

A Calcium/Calmodulin-dependent Activation of ERK1/2 Mediates JunD Phosphorylation and Induction of nur77 and20α-hsd Genes by Prostaglandin F2α in Ovarian Cells

Intracellular Ca²⁺Regulates Free-Running Circadian Clock OscillationIn Vivo

Mechanisms of seizure-induced ‘transcriptional channelopathy’ of hyperpolarization-activated cyclic nucleotide gated (HCN) channels

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The Ca2+/calmodulin system in neuronal hyperexcitability

Cited by 47 publications

References 69 publications

A Calcium/Calmodulin-dependent Activation of ERK1/2 Mediates JunD Phosphorylation and Induction of nur77 and20α-hsd Genes by Prostaglandin F2α in Ovarian Cells

A Calcium/Calmodulin-dependent Activation of ERK1/2 Mediates JunD Phosphorylation and Induction of nur77 and20α-hsd Genes by Prostaglandin F2α in Ovarian Cells

Intracellular Ca2+Regulates Free-Running Circadian Clock OscillationIn Vivo

Mechanisms of seizure-induced ‘transcriptional channelopathy’ of hyperpolarization-activated cyclic nucleotide gated (HCN) channels

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Intracellular Ca²⁺Regulates Free-Running Circadian Clock OscillationIn Vivo