Upregulation of Cav3.2 T-type calcium channels in adjacent intact L4 dorsal root ganglion neurons in neuropathic pain rats with L5 spinal nerve ligation

Liu, Qing-Ying; Chen, Wen; Cui, Shuang; Liao, Fei-Fei; Yi, Ming; Liu, Fengyu; Wan, You

doi:10.1016/j.neures.2018.04.002

Cited by 22 publications

(18 citation statements)

References 40 publications

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“…In these initial assays, SNL did not induce significant changes in the expression of the Ca V 3.2 channels 14 d after nerve ligation ( Fig. 6A), which disagrees with recent studies reporting an increase in the expression of these channels after injury or spinal nerve ligation (Shiue et al, 2016;Liu et al, 2019). Nevertheless, it is worth noting here that these results corresponded to what was observed from total cell lysates made from a preparation that included the spinal nerve, the DRG, and the dorsal root (not from the plasma membrane fraction only).…”

Section: Effect Of the Spinal Nerve Ligation On The Expression And Locontrasting

confidence: 97%

Cdk5-Dependent Phosphorylation of Ca_V3.2 T-Type Channels: Possible Role in Nerve Ligation-Induced Neuropathic Allodynia and the Compound Action Potential in Primary Afferent C Fibers

et al. 2019

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Voltage-gated T-type Ca 2ϩ (Ca V 3) channels regulate diverse physiological events, including neuronal excitability, and have been linked to several pathological conditions such as absence epilepsy, cardiovascular diseases, and neuropathic pain. It is also acknowledged that calcium/calmodulin-dependent protein kinase II and protein kinases A and C regulate the activity of T-type channels. Interestingly, peripheral nerve injury induces tactile allodynia and upregulates Ca V 3.2 channels and cyclin-dependent kinase 5 (Cdk5) in dorsal root ganglia (DRG) and spinal dorsal horn. Here, we report that recombinant Ca V 3.2 channels expressed in HEK293 cells are regulatory targets of Cdk5. Site-directed mutagenesis showed that the relevant sites for this regulation are residues S561 and S1987. We also found that Cdk5 may regulate Ca V 3.2 channel functional expression in rats with mechanical allodynia induced by spinal nerve ligation (SNL). Consequently, the Cdk5 inhibitor olomoucine affected the compound action potential recorded in the spinal nerves, as well as the paw withdrawal threshold. Likewise, Cdk5 expression was upregulated after SNL in the DRG. These findings unveil a novel mechanism for how phosphorylation may regulate Ca V 3.2 channels and suggest that increased channel activity by Cdk5-mediated phosphorylation after SNL contributes nerve injury-induced tactile allodynia.

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Section: Effect Of the Spinal Nerve Ligation On The Expression And Locontrasting

confidence: 97%

Cdk5-Dependent Phosphorylation of Ca_V3.2 T-Type Channels: Possible Role in Nerve Ligation-Induced Neuropathic Allodynia and the Compound Action Potential in Primary Afferent C Fibers

et al. 2019

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“…As expected, expression levels of Nav1.7 in the L4 DRG were significantly higher after SNL. This accords with findings of previous reports suggesting that proteins or mRNAs involved in nociception were upregulated in uninjured L4 DRGs after L5 SNL, including the Nav1.8, the T‐type calcium channel 3.2 and TRPV1 . Xin‐Hua et al found that expression levels of Nav1.3 and Nav1.8 mRNAs in bilateral L4 and L5 DRGs were elevated by selectively cutting off anterior root motor nerve fibers .…”

Section: Discussionsupporting

confidence: 92%

Voltage‐gated sodium channel 1.7 expression decreases in dorsal root ganglia in a spinal nerve ligation neuropathic pain model

Zhang

Yang

et al. 2019

The Kaohsiung J of Med Scie

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The role of the voltage-gated sodium channel 1.7 (Nav1.7) is unclear in models of neuropathic pain induced by nerve injury. In the present study, we measured expression levels of Nav1.7 in two distinct neuropathic pain models: spinal nerve ligation (SNL) and chronic constriction injury (CCI). In the SNL model, both mRNA and protein levels of Nav1.7 were markedly lower in the L5 dorsal root ganglia (DRG) but were significantly higher in the L4 DRG. Nav1.7 protein levels were notably higher in both L4 and L5 DRGs under CCI conditions. We found that excessive damage of L5 nerves such as SNL reduced expression levels of Nav1.7 in the injured L5 DRG and activated the adjacent uninjured DRG, resulting in Nav1.7 level increases in the adjacent L4 DRG. We confirmed again that Nav1.7 was closely related to neuropathic pain induced by nerve injury. More importantly, our results suggest that tracing the molecular changes exclusively in the L5 DRG in SNL model may not completely explain the pain mechanism; it is necessary to study the adjacent uninjured L4 DRG. K E Y W O R D S chronic constriction injury, dorsal root ganglia, neuropathic pain, spinal nerve ligation, voltagegated sodium channel 1.7

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“…In addition to expression studies, functional studies are also needed to investigate the physiological roles of these channels. There are many reports that increased membrane expression of the ion channel parallels functional up-regulation of the ion channel in neurons [35].…”

Section: Discussionmentioning

confidence: 99%

Role of Dysregulated Ion Channels in Sensory Neurons in Chronic Kidney Disease-Associated Pruritus

Momose¹,

Yabe²,

Chiba³

et al. 2019

Medicines

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Background: We investigated ion channels at the skin, including peripheral nerve endings, which serve as output machines and molecular integrators of many pruritic inputs mainly received by multiple G protein-coupled receptors (GPCRs). Methods: Based on the level of chronic kidney disease–associated pruritus (CKD-aP), subjects were divided into two groups: non-CKD-aP (no or slight pruritus; n = 12) and CKD-aP (mild, moderate, or severe pruritus; n = 11). Skin samples were obtained from the forearm or elbow during operations on arteriovenous fistulas. We measured ion channels expressed at the skin, including peripheral nerve endings by RT-PCR: Nav1.8, Kv1.4, Cav2.2, Cav3.2, BKCa, Anoctamin1, TRPV1, TRPA1, and ASIC. Results: Expression of Cav3.2, BKCa, and anoctamin1 was significantly elevated in patients with CKD-aP. On the other hand, expression of TRPV1 was significantly reduced in these patients. We observed no significant difference in the levels of Cav2.2 or ASIC between subjects with and without CKD-aP. TRPA1, Nav1.8, and Kv1.4 were not expressed. Conclusions: It was concluded that this greater difference in the expression of ion channels in the skin tissue including, specially cutaneous peripheral nerve endings in CKD patients with CKD-aP may increase generator potential related to itching.

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Upregulation of Cav3.2 T-type calcium channels in adjacent intact L4 dorsal root ganglion neurons in neuropathic pain rats with L5 spinal nerve ligation

Cited by 22 publications

References 40 publications

Cdk5-Dependent Phosphorylation of Ca_V3.2 T-Type Channels: Possible Role in Nerve Ligation-Induced Neuropathic Allodynia and the Compound Action Potential in Primary Afferent C Fibers

Cdk5-Dependent Phosphorylation of Ca_V3.2 T-Type Channels: Possible Role in Nerve Ligation-Induced Neuropathic Allodynia and the Compound Action Potential in Primary Afferent C Fibers

Voltage‐gated sodium channel 1.7 expression decreases in dorsal root ganglia in a spinal nerve ligation neuropathic pain model

Role of Dysregulated Ion Channels in Sensory Neurons in Chronic Kidney Disease-Associated Pruritus

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Upregulation of Cav3.2 T-type calcium channels in adjacent intact L4 dorsal root ganglion neurons in neuropathic pain rats with L5 spinal nerve ligation

Cited by 22 publications

References 40 publications

Cdk5-Dependent Phosphorylation of CaV3.2 T-Type Channels: Possible Role in Nerve Ligation-Induced Neuropathic Allodynia and the Compound Action Potential in Primary Afferent C Fibers

Cdk5-Dependent Phosphorylation of CaV3.2 T-Type Channels: Possible Role in Nerve Ligation-Induced Neuropathic Allodynia and the Compound Action Potential in Primary Afferent C Fibers

Voltage‐gated sodium channel 1.7 expression decreases in dorsal root ganglia in a spinal nerve ligation neuropathic pain model

Role of Dysregulated Ion Channels in Sensory Neurons in Chronic Kidney Disease-Associated Pruritus

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Cdk5-Dependent Phosphorylation of Ca_V3.2 T-Type Channels: Possible Role in Nerve Ligation-Induced Neuropathic Allodynia and the Compound Action Potential in Primary Afferent C Fibers

Cdk5-Dependent Phosphorylation of Ca_V3.2 T-Type Channels: Possible Role in Nerve Ligation-Induced Neuropathic Allodynia and the Compound Action Potential in Primary Afferent C Fibers