Ca<sub>v</sub>1.2 and Ca<sub>v</sub>1.3 L-type calcium channels regulate dopaminergic firing activity in the mouse ventral tegmental area

Liu, Yudan; Harding, Meghan; Pittman, Nicole; Doré, Jules J.E.; Striessnig, Jörg; Rajadhyaksha, Anjali M.; Chen, Xihua

doi:10.1152/jn.00757.2013

Cited by 62 publications

(52 citation statements)

References 53 publications

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“…LC and DMV have also been demonstrated to express Cav1.3 channels and to exhibit elevated mitochondria oxidative stress [43,94]. In contrast, VTA DA neurons, which are relatively spared in PD, are also autonomous pacemakers but have been shown to have modest Cav1 channel currents [66,97,98], robust cytosolic Ca 2+ buffering [56,99] and low mitochondrial oxidant stress. Additional studies are needed to determine whether there are other physiological phenotypes that contribute to vulnerability in PD.…”

Section: A Common At-risk Neuronal Phenotype In Pd?mentioning

confidence: 99%

Calcium and Parkinson's disease

Surmeier

Schumacker

Guzmán

et al. 2017

Biochemical and Biophysical Research Communications

164

146

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Parkinson’s disease (PD) is the second most common neurodegenerative disease in the world. Its causes are poorly understood and there is no proven therapeutic strategy for slowing disease progression. The core motor symptoms of PD are caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SNc). In these neurons, Ca2+entry through plasma membrane Cav1 channels drives a sustained feed-forward stimulation of mitochondrial oxidative phosphorylation. Although this design helps prevent bioenergetic failure when activity needs to be sustained, it leads to basal mitochondrial oxidant stress. Over decades, this basal oxidant stress could compromise mitochondrial function and increase mitophagy, resulting in increased vulnerability to other proteostatic stressors, like elevated alpha synuclein expression. Because this feedforward mechanism is no longer demanded by our lifestyle, it could be dispensed with. Indeed, use of dihydropyridines – negative allosteric modulators of Cav1 Ca2+ channels – comes with little or no effect on brain function but is associated with decreased risk and progression of PD. An ongoing, NIH sponsored, Phase 3 clinical trial in North America is testing the ability of one member of the dihydropyridine class (isradipine) to slow PD progression in early stage patients. The review summarizes the rationale for the trial and outlines some unanswered questions.

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Section: A Common At-risk Neuronal Phenotype In Pd?mentioning

confidence: 99%

Calcium and Parkinson's disease

Surmeier

Schumacker

Guzmán

et al. 2017

Biochemical and Biophysical Research Communications

164

146

View full text Add to dashboard Cite

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“…It also contributes to aversive learning and memory processes [Berger and Bartsch, 2014;Liu et al, 2014], and it has been linked to neurodegenerative disorders [Berger and Bartsch, 2014]. Mutations in this gene are considered among risk factors for ASD and intellectual disability, with both entailing language deficits [Pinggera et al, 2015].…”

Section: Sz and (The Evolution Of) Human Languagementioning

confidence: 99%

Schizophrenia and Human Self-Domestication: An Evolutionary Linguistics Approach

et al. 2017

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Schizophrenia (SZ) is a pervasive neurodevelopmental disorder that entails social and cognitive deficits, including marked language problems. Its complex multifactorial etiopathogenesis, including genetic and environmental factors, is still widely uncertain. SZ incidence has always been high and quite stable in human populations, across time and regardless of cultural implications, for unclear reasons. It has been hypothesized that SZ pathophysiology may involve the biological components that changed during the recent human evolutionary history, and led to our distinctive mode of cognition, which includes language skills. In this paper we explore this hypothesis, focusing on the self-domestication of the human species. This has been claimed to account for many human-specific distinctive traits, including aspects of our behavior and cognition, and to favor the emergence of complex languages through cultural evolution. The “domestication syndrome” in mammals comprises the constellation of traits exhibited by domesticated strains, seemingly resulting from the hypofunction of the neural crest. It is our intention to show that people with SZ exhibit more marked domesticated traits at the morphological, physiological, and behavioral levels. We also show that genes involved in domestication and neural crest development and function comprise nearly 20% of SZ candidates, most of which exhibit altered expression profiles in the brain of SZ patients, specifically in areas involved in language processing. Based on these observations, we conclude that SZ may represent an abnormal ontogenetic itinerary for the human faculty of language, resulting, at least in part, from changes in genes important for the domestication syndrome and primarily involving the neural crest.

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“…In particular, Ca V 1.3 and Ca V 1.2 have been extensively studied upstream of Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) and cAMP response element-binding protein (CREB) signaling pathways in neurons [20–22]. Furthermore, the lower-threshold L-type Ca V 1.3 channel is implicated in pace-making in dopaminergic neurons, and in neuroendocrine cells, such as adrenal chromaffin cells [23, 24]. Since L-type channels Ca V 1.2 and Ca V 1.3 are expressed with monoamine transporters in several excitable cells [23–29], determining a functional interaction between these two classes of proteins could constitute an additional molecular mechanism of AMPH action.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, the lower-threshold L-type Ca V 1.3 channel is implicated in pace-making in dopaminergic neurons, and in neuroendocrine cells, such as adrenal chromaffin cells [23, 24]. Since L-type channels Ca V 1.2 and Ca V 1.3 are expressed with monoamine transporters in several excitable cells [23–29], determining a functional interaction between these two classes of proteins could constitute an additional molecular mechanism of AMPH action.…”

Section: Introductionmentioning

confidence: 99%

Amphetamine activates calcium channels through dopamine transporter-mediated depolarization

et al. 2015

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Amphetamine (AMPH) and its more potent enantiomer S(+)AMPH are psychostimulants used therapeutically to treat attention deficit hyperactivity disorder and have significant abuse liability. AMPH is a dopamine transporter (DAT) substrate that inhibits dopamine (DA) uptake and is implicated in DA release. Furthermore, AMPH activates ionic currents through DAT that modify cell excitability presumably by modulating voltage-gated channel activity. Indeed, several studies suggest that monoamine transporter-induced depolarization opens voltage-gated Ca2+ channels (CaV), which would constitute an additional AMPH mechanism of action. In this study we co-express human DAT (hDAT) with Ca2+ channels that have decreasing sensitivity to membrane depolarization (CaV1.3, CaV1.2 or CaV2.2). Although S(+)AMPH is more potent than DA in transport-competition assays and inward-current generation, at saturating concentrations both substrates indirectly activate voltage-gated L-type Ca2+ channels (CaV1.3 and CaV1.2) but not the N-type Ca2+ channel (CaV2.2). Furthermore, the potency to achieve hDAT-CaV electrical coupling is dominated by the substrate affinity on hDAT, with negligible influence of L-type channel voltage sensitivity. In contrast, the maximal coupling-strength (defined as Ca2+ signal change per unit hDAT current) is influenced by CaV voltage sensitivity, which is greater in CaV1.3- than in CaV1.2-expressing cells. Moreover, relative to DA, S(+)AMPH showed greater coupling-strength at concentrations that induced relatively small hDAT-mediated currents. Therefore S(+)AMPH is not only more potent than DA at inducing hDAT-mediated L-type Ca2+ channel currents but is a better depolarizing agent since it produces tighter electrical coupling between hDAT-mediated depolarization and L-type Ca2+ channel activation.

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Ca_v1.2 and Ca_v1.3 L-type calcium channels regulate dopaminergic firing activity in the mouse ventral tegmental area

Cited by 62 publications

References 53 publications

Calcium and Parkinson's disease

Calcium and Parkinson's disease

Schizophrenia and Human Self-Domestication: An Evolutionary Linguistics Approach

Amphetamine activates calcium channels through dopamine transporter-mediated depolarization

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Cav1.2 and Cav1.3 L-type calcium channels regulate dopaminergic firing activity in the mouse ventral tegmental area

Cited by 62 publications

References 53 publications

Calcium and Parkinson's disease

Calcium and Parkinson's disease

Schizophrenia and Human Self-Domestication: An Evolutionary Linguistics Approach

Amphetamine activates calcium channels through dopamine transporter-mediated depolarization

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Product

Resources

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Ca_v1.2 and Ca_v1.3 L-type calcium channels regulate dopaminergic firing activity in the mouse ventral tegmental area