Regulation of voltage-gated Ca2+ currents by Ca2+/calmodulin-dependent protein kinase II in resting sensory neurons

Kostić, Sandra; Pan, Bin; Guo, Yuan; Yu, Hongwei; Sapunar, Damir; Kwok, Wai Meng; Hudmon, Andy; Wu, Hsiang‐En; Hogan, Quinn H.

doi:10.1016/j.mcn.2014.07.004

Cited by 11 publications

(26 citation statements)

References 45 publications

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“…Highly purified stocks of AAV8-EGFP-AIP and AAV8-EGFP vectors were generated by a helper virus-free system, followed by two cycles of CsCl 2 gradient purification, according to a previously described protocol (Tang et al, 2012). Final viral preparations were kept in PBS containing 5% sorbitol (Sigma-Aldrich) at Ϫ80°C.…”

Section: Aav Vector Productionmentioning

confidence: 99%

“…Final viral preparations were kept in PBS containing 5% sorbitol (Sigma-Aldrich) at Ϫ80°C. Encapsidated viral DNA was quantified against plasmid standards by a PicoGreen assay (Invitrogen) following denaturation of the purified AAV particles, and the physical titer was expressed as genome copy number per milliliter (GC/ml) (Tang et al, 2012). Titers of AAV8-EGFP-AIP and AAV8-CMV-EGFP were 9.84 ϫ 10 12 GC/ml and 2.11 ϫ 10 13 GC/ml, respectively.…”

Section: Aav Vector Productionmentioning

confidence: 99%

“…For cast immobilization (Guo et al, 2004), one hindlimb was placed in a synthetic resin cast lined with cotton that enclosed the metatarsals at its inferior-most extent and joined a circumferential component at the level of the abdomen, retaining the limb's normal standing posture, and maintained for 10 d.…”

Section: Sensory Deprivation Modelsmentioning

confidence: 99%

“…The underlying mechanisms contributing to adaptation have been less explored for the sense of touch than for the visual, olfactory, auditory, and proprioceptive systems (Torre et al, 1995). However, it is clear that touch is subject to use-dependent sensory adaptation because cutaneous mechanical hypersensitivity develops in the absence of normal sensory activation in rats (Guo et al, 2004) and human subjects (Aftanas and Zubek, 1963;Terkelsen et al, 2008), and reduced sensitivity follows prolonged cutaneous stimulation (Aftanas and Zubek, 1963).…”

Section: Introductionmentioning

confidence: 99%

“…In sensory neurons, use-dependent depression of intrinsic membrane excitability is mediated by activity-induced [Ca 2ϩ ] c elevation and requires the participation of Ca 2ϩ /calmodulin-dependent protein kinase II (CaMKII) (Tang et al, 2012). This ubiquitous Ca 2ϩ / CaM-activated kinase is highly abundant in the nervous system, including peripheral sensory neurons (Carlton, 2002;Kojundzic et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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CaMKII Controls Whether Touch Is Painful

Yu¹,

Pan²,

Weyer

et al. 2015

J. Neurosci.

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The sensation of touch is initiated when fast conducting low-threshold mechanoreceptors (A␤-LTMRs) generate impulses at their terminals in the skin. Plasticity in this system is evident in the process of adaption, in which a period of diminished sensitivity follows prior stimulation. CaMKII is an ideal candidate for mediating activity-dependent plasticity in touch because it shifts into an enhanced activation state after neuronal depolarizations and can thereby reflect past firing history. Here we show that sensory neuron CaMKII autophosphorylation encodes the level of A␤-LTMR activity in rat models of sensory deprivation (whisker clipping, tail suspension, casting). Blockade of CaMKII signaling limits normal adaptation of action potential generation in A␤-LTMRs in excised skin. CaMKII activity is also required for natural filtering of impulse trains as they travel through the sensory neuron T-junction in the DRG. Blockade of CaMKII selectively in presynaptic A␤-LTMRs removes dorsal horn inhibition that otherwise prevents A␤-LTMR input from activating nociceptive lamina I neurons. Together, these consequences of reduced CaMKII function in A␤-LTMRs cause low-intensity mechanical stimulation to produce pain behavior. We conclude that, without normal sensory activity to maintain adequate levels of CaMKII function, the touch pathway shifts into a pain system. In the clinical setting, sensory disuse may be a critical factor that enhances and prolongs chronic pain initiated by other conditions.

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Section: Aav Vector Productionmentioning

confidence: 99%

Section: Aav Vector Productionmentioning

confidence: 99%

Section: Sensory Deprivation Modelsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

CaMKII Controls Whether Touch Is Painful

Yu¹,

Pan²,

Weyer

et al. 2015

J. Neurosci.

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Colitis-induced bladder afferent neuronal activation is regulated by BDNF through PLCγ pathway

Xia

Shen

Hashmi

et al. 2016

Experimental Neurology

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Patients with inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS) often experience increased sensory responsiveness in the urinary bladder reflecting neurogenic bladder overactivity. Here we demonstrate that colitis-induced up-regulation of the phospholipase C gamma (PLCγ) pathway downstream of brain-derived neurotrophic factor (BDNF) in bladder afferent neurons in the dorsal root ganglia (DRG) plays essential roles in activating these neurons thereby leading to bladder hyperactivity. Upon induction of colitis with 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats, we found that the phosphorylation (activation) level of cAMP responsive element-binding (p-CREB) protein, a molecular switch of neuronal plasticity, was increased in specifically labeled bladder afferent neurons in the thoracolumbar and lumbosacral DRGs. In rats having reduced levels of BDNF (BDNF+/−), colitis failed to elevate CREB protein activity in bladder afferent neurons. Physiological examination also demonstrated that colitis-induced urinary frequency was not shown in BDNF+/− rats, implicating an essential role of BDNF in mediating colon-to-bladder sensory cross-sensitization. We further implemented in vivo and in vitro studies and demonstrated that BDNF-mediated colon-to-bladder sensory cross-activation involved the TrkB - PLCγ-calcium/calmodulin-dependent protein kinase II (CaMKII) cascade. In contrast, the PI3K/Akt pathway was not activated in bladder afferent neurons during colitis and was not involved in BDNF action in the DRG. Our results suggest that colon-to-bladder sensory cross-sensitization is regulated by specific signal transduction initiated by the up-regulation of BDNF in the DRG.

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Differential expression of CaMKII isoforms and overall kinase activity in rat dorsal root ganglia after injury

et al. 2015

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Ca2+/Calmodulin-dependent protein kinase II (CaMKII) decodes neuronal activity by translating cytoplasmic Ca2+ signals into kinase activity that regulates neuronal functions including excitability, gene expression, and synaptic transmission. Four genes lead to developmental and differential expression of CaMKII isoforms (α, β, γ, δ). We determined mRNA levels of these isoforms in the dorsal root ganglia (DRG) of adult rats with and without nerve injury in order to determine if differential expression of CaMKII isoforms may contribute to functional differences that follow injury. DRG neurons express mRNA for all four isoforms, and the relative abundance of CaMKII isoforms was γ>α>β=δ, based on the CT values. Following ligation of the 5th lumbar (L5) spinal nerve (SNL), the β isoform did not change, but mRNA levels of both the γ and α isoforms were reduced in the directly injured L5 neurons, and the α isoform was reduced in L4 neurons, compared to their contemporary controls. In contrast, expression of the δ isoform mRNA increased in L5 neurons. CaMKII protein decreased following nerve injury in both L4 and L5 populations. Total CaMKII activity measured under saturating Ca2+/CaM conditions was decreased in both L4 and L5 populations, while autonomous CaMKII activity determined in the absence of Ca2+ was selectively reduced in axotomized L5 neurons 21d after injury. Thus, loss of CaMKII signaling in sensory neurons after peripheral nerve injury may contribute to neuronal dysfunction and pain.

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Regulation of voltage-gated Ca2+ currents by Ca2+/calmodulin-dependent protein kinase II in resting sensory neurons

Cited by 11 publications

References 45 publications

CaMKII Controls Whether Touch Is Painful

CaMKII Controls Whether Touch Is Painful

Colitis-induced bladder afferent neuronal activation is regulated by BDNF through PLCγ pathway

Differential expression of CaMKII isoforms and overall kinase activity in rat dorsal root ganglia after injury

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