CaMKII inactivation by extracellular Ca2+ depletion in dorsal root ganglion neurons

Cohen, Jeffrey K.; Fields, R. Douglas

doi:10.1016/j.ceca.2006.01.005

Cited by 18 publications

(13 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The rapid chelation of extracellular calcium by BAPTA presumably decreases the amount of calcium in specific intracellular pools that continually drive CaMKII autophosphorylation in the face of significant basal phosphatase activity(ies) that can dephosphorylate Thr286 (Strack et al 1997b, Fukunaga et al 1993, Ishida et al 1998). These findings are consistent with prior studies in cultured neurons showing that removal of extracellular calcium profoundly decreases CaMKII autophosphorylation (Scholz & Palfrey 1998, Cohen & Fields 2006). We also found that extracellular calcium chelation decreases the phosphorylation of GluN2B and GluA1, key synaptic substrates of CaMKII (Hunt & Castillo 2012, Santos et al 2009), suggesting that basal CaMKII activity is driving the phosphorylation of physiological CaMKII substrates.…”

Section: Discussionsupporting

confidence: 93%

Differential CaMKII regulation by voltage-gated calcium channels in the striatum

Pasek

Wang

Colbran

2015

Molecular and Cellular Neuroscience

View full text Add to dashboard Cite

Calcium signaling regulates synaptic plasticity and many other functions in striatal medium spiny neurons to modulate basal ganglia function. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a major calcium-dependent signaling protein that couples calcium entry to diverse cellular changes. CaMKII activation results in autophosphorylation at Thr286 and sustained calcium-independent CaMKII activity after calcium signals dissipate. However, little is known about the mechanisms regulating striatal CaMKII. To address this, mouse brain slices were treated with pharmacological modulators of calcium channels and punches of dorsal striatum were immunoblotted for CaMKII Thr286 autophosphorylation as an index of CaMKII activation. KCl depolarization increased levels of CaMKII autophosphorylation ∼2-fold; this increase was blocked by an LTCC antagonist and was mimicked by treatment with pharmacological LTCC activators. The chelation of extracellular calcium robustly decreased basal CaMKII autophosphorylation within 5 min and increased levels of total CaMKII in cytosolic fractions, in addition to decreasing the phosphorylation of CaMKII sites in the GluN2B subunit of NMDA receptors and the GluA1 subunit of AMPA receptors. We also found that the maintenance of basal levels of CaMKII autophosphorylation requires low-voltage gated T-type calcium channels, but not LTCCs or R-type calcium channels. Our findings indicate that CaMKII activity is dynamically regulated by multiple calcium channels in the striatum thus coupling calcium entry to key downstream substrates.

show abstract

Section: Discussionsupporting

confidence: 93%

Differential CaMKII regulation by voltage-gated calcium channels in the striatum

Pasek

Wang

Colbran

2015

Molecular and Cellular Neuroscience

View full text Add to dashboard Cite

show abstract

“…Rhodamine-conjugated-CGRP-labeled neurons were then processed for immunofluorescence using the anti-TrkB receptor antibody. Control CaMKII immunofluorescence experiments performed on CGRP-treated neurons treated with CaMK inhibitors or incubated for 1 h in Ca 2ϩ -free medium (24) produced no signal (supplemental Fig. 1, A and C).…”

Section: Methodsmentioning

confidence: 99%

Mechanisms Mediating the Enhanced Gene Transcription of P2X3 Receptor by Calcitonin Gene-related Peptide in Trigeminal Sensory Neurons

Simonetti

Giniatullin

Fabbretti

2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

The molecular mechanisms underlying migraine pain remain unclear and probably require sustained facilitation in pain-sensing P2X 3 receptors gated by extracellular ATP in nociceptive sensory neurons. The major migraine mediator calcitonin generelated peptide (CGRP) is known to sensitize P2X 3 receptors to increase impulse flow to brainstem trigeminal nuclei. This process is mediated via changes in the expression and function of P2X 3 receptors initially through enhanced trafficking and, later, perhaps through augmented synthesis of P2X 3 receptors. To clarify the mechanisms responsible for CGRP-evoked long lasting alterations in P2X 3 receptors, we used as a model mouse trigeminal ganglion neurons in culture. CGRP activated Ca 2؉ -calmodulin-dependent kinase II, which became localized to the perimembrane region and neuronal processes, a phenomenon already apparent after 30 min and accompanied by a parallel increase in cAMP-response element-binding protein (CREB) phosphorylation and nuclear translocation. These effects triggered increased P2X 3 receptor transcription and were prevented by expressing a dominant negative form of CREB. Increased P2X 3 receptor synthesis was partly mediated by endogenous brain-derived neurotrophic factor (BDNF) because of its block by anti-BDNF antibodies and mimicry by exogenous BDNF. Immunocytochemistry experiments indicated distinct subpopulations of BDNF-or CGRP-sensitive trigeminal neurons with only partial overlap. The present data indicate a novel mechanism for enhancing P2X 3 receptor expression and function in trigeminal sensory neurons by CGRP via CREB phosphorylation. BDNF was an intermediate to extend the sensitizing effect of CGRP also to CGRP-insensitive neurons. This combinatorial action could serve as a powerful process to amplify and prolong pain mediated by P2X 3 receptors.Sensitization of sensory neurons represents the key phenomenon for generating chronic pain that remains relatively refractory to standard treatment (1). Current theories predict that chronic pain is brought about by a gain in the expression and function of sensory nociceptors that enhance their signal flow to the brain to ensure the long lasting nature of this process (2). Clarification of the novel gene expression profiles associated to pain should, therefore, be useful to target emerging molecules (and mechanisms) and for designing new analgesics. Previous studies (3) aimed at detecting changes in transcriptome patterns during pain conditions have provided only a limited description of the global alterations because of the complexity of pain pathologies and signal pathways.Migraine is a classical example of chronic, relapsing pain triggered by local release of endogenous pain mediators, such as the neuropeptide calcitonin gene-related peptide (CGRP) 2 (4, 5) that induces long lasting trigeminal neuronal sensitization (6) and novel gene transcription in sensory neurons (7-9). CGRPmediated signals are transduced at the cell membrane by activation of a G-protein-coupled receptor complex (composed b...

show abstract

“…It has been previously demonstrated in cultured nodose neurons that the CCK-induced increase in cytosolic calcium concentrations is dependent on extracellular calcium influx rather than mobilization on intracellular stores (49). In neurons of the dorsal root ganglia, such a decrease in CaMKII autophosphorylation has been reported in vitro by depleting extracellular calcium (50). The significance of this observation in the present study needs further investigation.…”

Section: Discussionmentioning

confidence: 92%

Loss of Vagal Sensitivity to Cholecystokinin in Rats Born with Intrauterine Growth Retardation and Consequence on Food Intake

et al. 2017

View full text Add to dashboard Cite

Perinatal malnutrition is associated with low birth weight and an increased risk of developing metabolic syndrome in adulthood. Modification of food intake (FI) regulation was observed in adult rats born with intrauterine growth retardation induced by maternal dietary protein restriction during gestation and maintained restricted until weaning. Gastrointestinal peptides and particularly cholecystokinin (CCK) play a major role in short-term regulation of FI by relaying digestive signals to the hindbrain via the vagal afferent nerve (VAN). We hypothesized that vagal sensitivity to CCK could be affected in rats suffering from undernutrition [low protein (LP)] during fetal and postnatal life, leading to an altered gut–brain communication and impacting satiation. Our aim was to study short-term FI along with signals of appetite and satiation in adult LP rats compared to control rats. The dose–response to CCK injection was investigated on FI as well as the associated signaling pathways activated in nodose ganglia. We showed that LP rats have a reduced first-meal satiety ratio after a fasting period associated to a higher postprandial plasmatic CCK release, a reduced sensitivity to CCK when injected at low concentration and a reduced presence of CCK-1 receptor in nodose ganglia. Accordingly, the lower basal and CCK-induced phosphorylation of calcium/calmodulin-dependent protein kinase in nodose ganglia of LP rats could reflect an under-expressed vanilloid family of transient receptor potential cation channels on VAN. Altogether, the present data demonstrated a reduced vagal sensitivity to CCK in LP rats at adulthood, which could contribute to deregulation of FI reported in this model.

show abstract

CaMKII inactivation by extracellular Ca2+ depletion in dorsal root ganglion neurons

Cited by 18 publications

References 53 publications

Differential CaMKII regulation by voltage-gated calcium channels in the striatum

Differential CaMKII regulation by voltage-gated calcium channels in the striatum

Mechanisms Mediating the Enhanced Gene Transcription of P2X3 Receptor by Calcitonin Gene-related Peptide in Trigeminal Sensory Neurons

Loss of Vagal Sensitivity to Cholecystokinin in Rats Born with Intrauterine Growth Retardation and Consequence on Food Intake

Contact Info

Product

Resources

About