TRPC4 ion channel protein is selectively expressed in a subpopulation of dopamine neurons in the ventral tegmental area

Illig, Kurt R.; Varnell, Andrew; Ostertag, Eric; Klipec, William D.; Cooper, Donald

doi:10.1038/npre.2011.6577.1

Cited by 6 publications

(3 citation statements)

References 4 publications

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“…The mRNA of TRPC4 was found to be highly abundant in the corticolimbic regions of the brain (Fowler et al, 2007). In addition, it is also present in midbrain dopaminergic neurons of the ventral tegmental area and the substantia nigra (Illig, Varnell, Ostertag, Klipec, & Cooper, 2012). TRPC4 mRNA is also highly enriched in bones (Riccio et al, 2002).…”

Section: Tissue Distribution and Multimerization Of Trpcsmentioning

confidence: 96%

TRPC channels: Structure, function, regulation and recent advances in small molecular probes

Wang

Cheng

Tian

et al. 2020

Pharmacology & Therapeutics

149

152

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Transient receptor potential canonical (TRPC) channels constitute a group of receptor-operated calcium-permeable nonselective cation channels of the TRP superfamily. The seven mammalian TRPC members, which can be further divided into four subgroups (TRPC1, TRPC2, TRPC4/5, and TRPC3/6/7) based on their amino acid sequences and functional similarities, contribute to a broad spectrum of cellular functions and physiological roles. Studies have revealed complexity of their regulation involving several components of the phospholipase C pathway, G i and G o proteins, and internal Ca 2+ stores. Recent advances in cryogenic electron microscopy have provided several high-resolution structures of TRPC channels. Growing evidence demonstrates the involvement of TRPC channels in diseases, particularly the link between genetic mutations of TRPC6 and familial

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Section: Tissue Distribution and Multimerization Of Trpcsmentioning

confidence: 96%

TRPC channels: Structure, function, regulation and recent advances in small molecular probes

Wang

Cheng

Tian

et al. 2020

Pharmacology & Therapeutics

149

152

View full text Add to dashboard Cite

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“…Copper transmembrane transporter (Braiterman et al, 2014) FRDs TRPC4 Calcium channel Forms a calcium-permeable cation channel, which plays a role in multiple processes including neurotransmitter release. Expressed in midbrain dopamine neurons and affects behavioural traits such as attention span and sociability (Illig et al, 2011;Rasmus et al, 2011). Involved in lung endothelial permeability (Tiruppathi et al, 2002).…”

Section: Frds Atp7b Calcium Channelmentioning

confidence: 99%

Human‐modified canids in human‐modified landscapes: The evolutionary consequences of hybridization for grey wolves and free‐ranging domestic dogs

Pilot

Moura

Охлопков

et al. 2021

Evolutionary Applications

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Introgressive hybridization between domestic animals and their wild relatives is an indirect form of human-induced evolution, altering gene pools and phenotypic traits of wild and domestic populations. Although this process is well documented in many taxa, its evolutionary consequences are poorly understood. In this study, we assess introgression patterns in admixed populations of Eurasian wolves and free-ranging domestic dogs (FRDs), identifying chromosomal regions with significantly overrepresented hybrid ancestry and assessing whether genes located within these regions show signatures of selection. Although the dog admixture proportion in West Eurasian wolves (2.7%) was greater than the wolf admixture proportion in FRDs (0.75%), the number and average length of chromosomal blocks showing significant overrepresentation of hybrid ancestry were smaller in wolves than FRDs. In wolves, 6% of genes located within these blocks showed signatures of positive selection compared to 23% in FRDs. We found that introgression from wolves may provide a considerable adaptive advantage to FRDs, counterbalancing some of the negative effects of domestication, which can include reduced genetic diversity and excessive tameness. In wolves, introgression from FRDs is mostly driven by drift, with a small number of positively selected genes associated with brain function and behaviour. The predominance of drift may be the consequence of small effective size of wolf populations, which reduces efficiency of selection for weakly advantageous or against weakly disadvantageous introgressed variants. Small wolf population sizes result largely from human-induced habitat loss and hunting, thus linking introgression rates to anthropogenic processes.Our results imply that maintenance of large population sizes should be an important element of wolf management strategies aimed at reducing introgression rates of dogderived variants.

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“…One possible explanation for the increased rheobase is an adapted function and/ or expression of factors supporting intrinsic excitability. DA cell firing properties and responsivity have been shown to rely on several ion channel functions and other postsynaptic mechanisms sensitive to drugs, including opioids [90][91][92][93][94][95] . Potassium current alterations may be the most parsimonious candidate, being an opioid-sensitive direct modulator of intrinsic excitability 96 .…”

Section: Discussionmentioning

confidence: 99%

Protracted morphine withdrawal corresponds with sex-specific alterations to motivated behavior and mesoaccumbal subcircuit dopamine cell plasticity

Gomez¹,

Kahl²,

Brettingen³

et al. 2023

Preprint

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Background: Opioid use disorder is associated with enduring psychological withdrawal symptoms believed to contribute to drug abuse. Amongst these are shifts in motivational states, wherein pursuit of drug consumption exceeds that of non-drug rewards, reinforcing escalated opioid use and relapse vulnerability. A critical regulator of behavioral reinforcement, the mesoaccumbal dopamine (DA) system is thought to be both necessary and sufficient for opioid motivation. However, previous research into its involvement in opioid withdrawal has been limited to acute vs protracted timepoints, global neuroadaptations vs those in subcircuits, and overwhelmingly focused on males vs females. Methods: Evaluations of effort-based motivated behavior for both sucrose and morphine reward were combined with patch clamp electrophysiological assessments of synaptic plasticity within lateral vs medial DA neurons projecting to the lateral vs medial nucleus accumbens shell during protracted morphine withdrawal in male and female mice. Further effects of mesoaccumbal subcircuit inhibition on motivated behavior for sucrose were also measured. Results: Protracted morphine withdrawal was found to be associated with elevations in morphine seeking, intake, and motivation compared to saline controls in both sexes. Escalation of intake was paralleled by a male-exclusive reduction in motivation for the non-drug reward, sucrose. Male-exclusive neuroadaptations during protracted withdrawal were also found, with reductions in neuronal excitability and increased inhibitory (GABAAR-dependent) synaptic transmission found in lateral ventral tegmental area (VTA) DA neurons projecting to the lateral nucleus accumbens shell, though not in medial DA projections to the medial shell. Finally, chemogenetic inhibition of the lateral but not medial subcircuit was found to significantly reduce motivated responding for sucrose in male morphine-naive mice. Conclusions: These data suggest that protracted opioid withdrawal is associated with a sex-independent increase in opioid consumption and motivation. They also suggest that male-specific reductions in motivation for non-drug reward during protracted withdrawal may be driven by a hypoactive state in a lateral mesoaccumbal DA subcircuit driven in part by increased inhibition of DA cells. These insights may be useful in development of therapies that temper withdrawal-associated psychological states predisposed towards prolonged and escalated opioid intake, a major treatment goal for OUD patients.

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TRPC4 ion channel protein is selectively expressed in a subpopulation of dopamine neurons in the ventral tegmental area

Cited by 6 publications

References 4 publications

TRPC channels: Structure, function, regulation and recent advances in small molecular probes

TRPC channels: Structure, function, regulation and recent advances in small molecular probes

Human‐modified canids in human‐modified landscapes: The evolutionary consequences of hybridization for grey wolves and free‐ranging domestic dogs

Protracted morphine withdrawal corresponds with sex-specific alterations to motivated behavior and mesoaccumbal subcircuit dopamine cell plasticity

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