Activity-dependent regulation of T-type calcium channels by submembrane calcium ions

Cazade, Magali; Bidaud, Isabelle; Lory, Philippe; Chemin, Jean

doi:10.7554/elife.22331

Cited by 27 publications

(25 citation statements)

References 70 publications

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“…Previous studies have described irreversible T‐type Ca 2+ current inhibition by low concentrations of TRPV1‐agonists in DRG neurons (Comunanza et al, ; Kerckhove et al, ). In this study, we show that this inhibition depends strictly on Ca 2+ , likely via Ca 2+ entry through capsaicin‐activated TRPV1 triggering intracellular feedback mechanisms as proposed elsewhere (Cazade et al, ; Comunanza et al, ; Kerckhove et al, ). Therefore, in tissues where TRPV1 and Ca v 3 channels coexist, low concentrations of TRPV1 activators (AM404 and capsaicin) irreversibly decrease T‐type current by a TRPV1‐mediated intracellular Ca 2+ increase.…”

Section: Discussionsupporting

confidence: 82%

“…Previous studies have described irreversible T-type Ca 2+ current inhibition by low concentrations of TRPV1-agonists in DRG neurons (Comunanza et al, 2011;Kerckhove et al, 2014). In this study, we show that this inhibition depends strictly on Ca 2+ , likely via Ca 2+ entry through capsaicinactivated TRPV1 triggering intracellular feedback mechanisms as proposed elsewhere (Cazade et al, 2017;Comunanza et al, 2011;Kerckhove et al, 2014). Therefore, in tissues where TRPV1 The kinetics of block by capsaicin, A-889425, and BCTC were amenable to IC 50 determination (Figure 2c), whereas capsazepine's kinetics were too slow for reliable determination of an IC 50 , hence we estimated its K D from on and off rates of block (Table 2).…”

Section: Trpv1-active Compounds Inhibit Ca V 3 Channels Directlysupporting

confidence: 83%

“…It has been suggested that the modulation of LVA and high voltage-activated calcium currents in DRG neurons induced by a lowconcentration capsaicin occurs via a TRPV1-mediated mechanism (Comunanza, Carbone, Marcantoni, Sher, & Ursu, 2011;Kerckhove et al, 2014;Wu, Chen, & Pan, 2005). This has recently been shown to occur via an intracellular calcium-dependent mechanism (Cazade, Bidaud, Lory, & Chemin, 2017;Comunanza et al, 2011), leading to inhibition of Ca v 3-mediated currents, caused by the influx of Ca 2+ through activated TRPV1. To date, the mechanism of direct capsaicin inhibition of Ca v 3 channels has not been addressed.…”

mentioning

confidence: 99%

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Analgesic transient receptor potential vanilloid‐1‐active compounds inhibit native and recombinant T‐type calcium channels

McArthur

Finol‐Urdaneta

Adams

2019

British J Pharmacology

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Background and Purpose T‐type calcium (Cav3) and transient receptor potential vanilloid‐1 (TRPV1) channels play central roles in the control of excitability in the peripheral nervous system and are regarded as potential therapeutic pain targets. Modulators that either activate or inhibit TRPV1‐mediated currents display analgesic properties in various pain models despite opposing effects on their connate target, TRPV1. We explored the effects of TRPV1‐active compounds on Cav3‐mediated currents. Experimental Approach Whole‐cell patch clamp recordings were used to examine the effects of TRPV1‐active compounds on rat dorsal root ganglion low voltage‐activated calcium currents and recombinant Cav3 isoforms in expression systems. Key Results The classical TRPV1 agonist capsaicin as well as TRPV1 antagonists A‐889425, BCTC, and capsazepine directly inhibited Cav3 channels. These compounds altered the voltage‐dependence of activation and inactivation of Cav3 channels and delayed their recovery from inactivation, leading to a concomitant decrease in T‐type current availability. The TRPV1 antagonist capsazepine potently inhibited Cav3.1 and 3.2 channels (KD < 120 nM), as demonstrated by its slow off rate. In contrast, neither the TRPV1 agonists, Palvanil and resiniferatoxin, nor the TRPV1 antagonist AMG9810 modulated Cav3‐mediated currents. Conclusions and Implications Analgesic TRPV1‐active compounds inhibit Cav3 currents in native and heterologous systems. Hence, their analgesic effects may not be exclusively attributed to their actions on TRPV1, which has important implications in the current understanding of nociceptive pathways. Importantly, our results highlight the need for attention in the experimental design used to address the analgesic properties of Cav3 channel inhibitors.

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Section: Discussionsupporting

confidence: 82%

Section: Trpv1-active Compounds Inhibit Ca V 3 Channels Directlysupporting

confidence: 83%

mentioning

confidence: 99%

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Analgesic transient receptor potential vanilloid‐1‐active compounds inhibit native and recombinant T‐type calcium channels

McArthur

Finol‐Urdaneta

Adams

2019

British J Pharmacology

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“…T-type calcium channels are low voltage-activated calcium channels that transiently open to evoke tiny Ca 2+ currents (reviewed in Perez-Reyes, 2003 ). T-type calcium channels regulate calcium influx from the extracellular region by opening the calcium channel ( Cazade et al ., 2017 ), or activating calcium-induced calcium release from the internal calcium source ( Kitchens et al ., 2003 ; Coulon et al ., 2009 ). These results suggest a critical role for T-type calcium channels in regulating intracellular calcium homeostasis and maintaining cellular function ( Assandri et al ., 1999 ; Chemin et al ., 2000 ; Cazade et al ., 2017 ).…”

Section: Introductionmentioning

confidence: 99%

T-Type Calcium Channels Are Required to Maintain Viability of Neural Progenitor Cells

Lee

Kim

et al. 2018

Biomol Ther (Seoul)

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T-type calcium channels are low voltage-activated calcium channels that evoke small and transient calcium currents. Recently, T-type calcium channels have been implicated in neurodevelopmental disorders such as autism spectrum disorder and neural tube defects. However, their function during embryonic development is largely unknown. Here, we investigated the function and expression of T-type calcium channels in embryonic neural progenitor cells (NPCs). First, we compared the expression of T-type calcium channel subtypes (CaV3.1, 3.2, and 3.3) in NPCs and differentiated neural cells (neurons and astrocytes). We detected all subtypes in neurons but not in astrocytes. In NPCs, CaV3.1 was the dominant subtype, whereas CaV3.2 was weakly expressed, and CaV3.3 was not detected. Next, we determined CaV3.1 expression levels in the cortex during early brain development. Expression levels of CaV3.1 in the embryonic period were transiently decreased during the perinatal period and increased at postnatal day 11. We then pharmacologically blocked T-type calcium channels to determine the effects in neuronal cells. The blockade of T-type calcium channels reduced cell viability, and induced apoptotic cell death in NPCs but not in differentiated astrocytes. Furthermore, blocking T-type calcium channels rapidly reduced AKT-phosphorylation (Ser473) and GSK3β-phosphorylation (Ser9). Our results suggest that T-type calcium channels play essential roles in maintaining NPC viability, and T-type calcium channel blockers are toxic to embryonic neural cells, and may potentially be responsible for neurodevelopmental disorders.

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“…T-type calcium channels are low voltage-activated calcium channels that transiently open to evoke tiny Ca 2+ currents (reviewed in (15)). T-type calcium channels regulate calcium influx from the extracellular region by opening the calcium channel (21), or activating calcium-induced calcium release from the internal calcium source (22,23). These results suggest a critical role for T-type calcium channels in regulating intracellular calcium homeostasis and maintaining cellular function (21,24,25).…”

Section: Discussionmentioning

confidence: 86%

TAF1-gene editing impairs Purkinje cell morphology and function

Janakiraman

Moutal

et al. 2019

Preprint

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TAF1 intellectual disability syndrome is an X-linked disorder caused by loss-of-function mutations in the TAF1 gene. How these mutations cause dysmorphology, hypotonia, intellectual and motor defects is unknown. Mouse models which have embryonically targeted TAF1 have failed, possibly due to TAF1 being essential for viability, preferentially expressed in early brain development, and intolerant of mutation. Novel animal models are valuable tools for understanding neuronal pathology. Here, we report the development and characterization of a novel animal model for TAF1 ID syndrome in which the TAF1 gene is deleted in embryonic rats using clustered regularly interspaced short palindromic repeats (CRISPR) associated protein 9 (Cas9) technology and somatic brain transgenesis mediated by lentiviral transduction. Rat pups, post-natal day 3, were subjected to intracerebroventricular (ICV) injection of either gRNA-control or gRNA-TAF1 vectors. Rats were subjected to a battery of behavioral tests followed by histopathological analyses of brains at post-natal day 14 and day 35. TAF1-edited rats exhibited behavioral deficits at both the neonatal and juvenile stages of development. Deletion of TAF1 lead to a hypoplasia and loss of the Purkinje cells. Abnormal motor symptoms in TAF1-edited rats were associated with irregular cerebellar output caused by changes in the intrinsic activity of the Purkinje cells. Immunostaining revealed a reduction in the expression of the CaV3.1 T-type calcium channel. This animal model provides a powerful new tool for studies of neuronal dysfunction in conditions associated with TAF1 abnormalities and should prove useful for developing therapeutic strategies to treat TAF1 ID syndrome. Intellectual disability (ID) syndrome is an X-linked rare disorder caused by loss-of-function mutations in the TAF1 gene. There is no animal model for understanding neuronal pathology and to facilitate development of new therapeutics for this X-linked intellectual disability syndrome. Novel animal models are valuable tools for understanding neuronal pathology and to facilitate development of new therapeutics for diseases. Here we developed a novel animal model for TAF1 ID syndrome in which the TAF1 gene is deleted by CRISPR-Cas9 editing and lentiviral transduction. This animal model provides a powerful new tool for studies of neuronal dysfunction associated with TAF1 abnormalities and should prove useful for developing therapeutic strategies to treat TAF1 ID syndrome.

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Activity-dependent regulation of T-type calcium channels by submembrane calcium ions

Cited by 27 publications

References 70 publications

Analgesic transient receptor potential vanilloid‐1‐active compounds inhibit native and recombinant T‐type calcium channels

Analgesic transient receptor potential vanilloid‐1‐active compounds inhibit native and recombinant T‐type calcium channels

T-Type Calcium Channels Are Required to Maintain Viability of Neural Progenitor Cells

TAF1-gene editing impairs Purkinje cell morphology and function

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