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Calcium channels dopamine transporter

Johanna Wagner, Franca Vulinović, Anne Grünewald, Marcus M Unger, Jens C Möller, Christine Klein, Patrick P Michel, Vincent Ries, Wolfgang H Oertel, Daniel Alvarez-Fischer
The polypeptide ghrelin is an endogenous ligand at the growth hormone secretagogue receptor 1a. To ghrelin multiple functions have been ascribed including promotion of gastrointestinal motility. Postprandial ghrelin levels have been reported to be reduced in patients suffering from Parkinson disease (PD). Experimental studies revealed neuroprotective effects of ghrelin in different PD models. The purpose of the present study was (i) to further elucidate the mechanism underlying the neuroprotective action of ghrelin and (ii) to determine whether these effects occur with both the acylated and the unacylated form...
December 4, 2017: Neuroscience
G Cristina Brailoiu, Elena Deliu, Jeffrey L Barr, Linda M Console-Bram, Alexandra M Ciuciu, Mary E Abood, Ellen M Unterwald, Eugen Brailoiu
BACKGROUND: HIV-1 infection and drug abuse are frequently co-morbid and their association greatly increases the severity of HIV-1-induced neuropathology. While nucleus accumbens (NAcc) function is severely perturbed by drugs of abuse, little is known about how HIV-1 infection affects NAcc. METHODS: We used calcium and voltage imaging to investigate the effect of HIV-1 trans-activator of transcription (Tat) on rat NAcc. Based on previous neuronal studies, we hypothesized that Tat modulates intracellular Ca2+ homeostasis of NAcc neurons...
September 1, 2017: Drug and Alcohol Dependence
Ernesto Solis, John S Partilla, Farhana Sakloth, Iwona Ruchala, Kathryn L Schwienteck, Louis J De Felice, Jose M Eltit, Richard A Glennon, S Stevens Negus, Michael H Baumann
Clandestine chemists synthesize novel stimulant drugs by exploiting structural templates known to target monoamine transporters for dopamine, norepinephrine, and serotonin (DAT, NET, and SERT, respectively). 4-Methylamphetamine (4-MA) is an emerging drug of abuse that interacts with transporters, but limited structure-activity data are available for its analogs. Here we employed uptake and release assays in rat brain synaptosomes, voltage-clamp current measurements in cells expressing transporters, and calcium flux assays in cells coexpressing transporters and calcium channels to study the effects of increasing N-alkyl chain length of 4-MA on interactions at DAT, NET, and SERT...
September 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
C E Terrillion, D T Dao, R Cachope, M K Lobo, A C Puche, J F Cheer, T D Gould
Genetic variation in CACNA1C, which codes for the L-type calcium channel (LTCC) Cav 1.2, is associated with clinical diagnoses of bipolar disorder, depression and schizophrenia. Dysregulation of the mesolimbic-dopamine (ML-DA) system is linked to these syndromes and LTCCs are required for normal DAergic neurotransmission between the ventral tegmental area (VTA) and nucleus accumbens (NAc). It is unclear, however, how variations in CACNA1C genotype, and potential subsequent changes in expression levels in these regions, modify risk...
June 2017: Genes, Brain, and Behavior
Plamena R Angelova, Andrey Y Abramov
The major energy generator in the cell - mitochondria produce reactive oxygen species as a by-product of a number of enzymatic reactions and the production of ATP. Emerging evidence suggests that mitochondrial ROS regulate diverse physiological parameters and that dysregulated ROS signalling may contribute to a development of processes which lead to human diseases. ROS produced in mitochondrial enzymes are triggers of monoamine-induced calcium signal in astrocytes, playing important role in physiological and pathophysiological response to dopamine...
November 2016: Free Radical Biology & Medicine
Qiong-Yin Fan, Rui Xue, Ying Li, Ting-Ting Zhang, Xin-Hua He, Shi-Yong Fan, Yun-Feng Li, Bo-Hua Zhong, You-Zhi Zhang, Jin Li
AIMS: The present study was conducted to evaluate the antidepressant-like effects of ZBH2012001, a novel potential serotonin and norepinephrine reuptake inhibitor (SNRI). METHODS: Competitive binding assays, calcium flow, and cAMP detection methods were used to determine the affinity of ZBH2012001 for serotonin transporters (SERTs) and norepinephrine transporters (NETs), as well as its selectivity over dopamine transporters (DATs) and 16 other G-protein-coupled receptors (GPCRs) or iron channels...
August 2016: CNS Neuroscience & Therapeutics
Ye Zhang, Hongmei Ren, Xi Lu, Duofen He, Yu Han, Hongyong Wang, Chunyu Zeng, Weibin Shi
BACKGROUND: Ion transport in the renal proximal tubule (RPT), which is increased in essential hypertension, is regulated by numerous hormones and humoral factors, including insulin and dopamine. Activation of dopamine receptor inhibits sodium reabsorption, whereas activation of insulin receptor increases sodium reabsorption in RPTs, and hyperinsulinemic animals and patients have defective renal dopaminergic system. We presume that there is an inhibition of D4 receptor on insulin receptor expression and effect, and the regulation is lost in spontaneously hypertensive rats (SHRs)...
April 22, 2016: Journal of the American Heart Association
Trayambak Pathak, Tarjani Agrawal, Shlesha Richhariya, Sufia Sadaf, Gaiti Hasan
UNLABELLED: Store operated calcium entry (SOCE) is thought to primarily regulate calcium homeostasis in neurons. Subsequent to identification of Orai as the SOCE channel in nonexcitable cells, investigation of Orai function in neurons demonstrated a requirement for SOCE in Drosophila flight. Here, by analysis of an Orai mutant and by controlled expression of a dominant-negative Drosophila Orai transgene, we show that Orai-mediated SOCE is required in dopaminergic interneurons of the flight circuit during pupal development...
October 7, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Roberto De Luca, Tatsiana Suvorava, Danqing Yang, Wilhelm Baumgärtel, Georg Kojda, Helmut L Haas, Olga A Sergeeva
Using a reporter mouse model with expression of the tomato fluorescent protein under the dopamine transporter promoter (Tmt-DAT) we discovered a new group of neurons in the histaminergic tuberomamillary nucleus (TMN), which, in contrast to tuberoinfundibular dopaminergic neurons of the dorsomedial arcuate nucleus, do not express tyrosine hydroxylase but can synthesize and store dopamine. Tmt-DAT neurons located within TMN share electrophysiological properties with histaminergic neurons: spontaneous firing at a membrane potential around -50 mV and presence of hyperpolarization-activated cyclic nucleotide-gated ion channels...
July 2016: Neuropharmacology
Krasnodara N Cameron, Ernesto Solis, Iwona Ruchala, Louis J De Felice, Jose M Eltit
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 Ca(2+) channels (CaV), which would constitute an additional AMPH mechanism of action...
November 2015: Cell Calcium
Amanda L Sharpe, Erika Varela, Lynne Bettinger, Michael J Beckstead
BACKGROUND: Methamphetamine is a psychomotor stimulant with abuse liability and a substrate for catecholamine uptake transporters. Acute methamphetamine elevates extracellular dopamine, which in the midbrain can activate D2 autoreceptors to increase a G-protein gated inwardly rectifying potassium (GIRK) conductance that inhibits dopamine neuron firing. These studies examined the neurophysiological consequences of methamphetamine self-administration on GIRK channel-mediated currents in dopaminergic neurons in the substantia nigra and ventral tegmental area...
March 2015: International Journal of Neuropsychopharmacology
Richard Brandon Goertz, Matthew J Wanat, Jorge A Gomez, Zeliene J Brown, Paul E M Phillips, Carlos A Paladini
Cocaine reinforcement is mediated by increased extracellular dopamine levels in the forebrain. This neurochemical effect was thought to require inhibition of dopamine reuptake, but cocaine is still reinforcing even in the absence of the dopamine transporter. Here, we demonstrate that the rapid elevation in dopamine levels and motor activity elicited by cocaine involves α1 receptor activation within the ventral midbrain. Activation of α1 receptors increases dopaminergic neuron burst firing by decreasing the calcium-activated potassium channel current (SK), as well as elevates dopaminergic neuron pacemaker firing through modulation of both SK and the hyperpolarization-activated cation currents (Ih)...
April 2015: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Jennilee Davidson, Michael D Cusimano, William G Bendena
It is estimated that 2% of the population from industrialized countries live with lifelong disabilities resulting from traumatic brain injury (TBI) and roughly one in four adults are unable to return to work 1 year after injury because of physical or mental disabilities. TBI is a significant public health issue that causes substantial physical and economical repercussions for the individual and society. Electronic databases (PubMed, Web of Science, Google Scholar) were searched with the keywords traumatic brain injury, TBI, genes and TBI, TBI outcome, head injury...
August 2015: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
Iwona Ruchala, Vanessa Cabra, Ernesto Solis, Richard A Glennon, Louis J De Felice, Jose M Eltit
Monoamine transporters have been implicated in dopamine or serotonin release in response to abused drugs such as methamphetamine or ecstasy (MDMA). In addition, monoamine transporters show substrate-induced inward currents that may modulate excitability and Ca(2+) mobilization, which could also contribute to neurotransmitter release. How monoamine transporters modulate Ca(2+) permeability is currently unknown. We investigate the functional interaction between the human serotonin transporter (hSERT) and voltage-gated Ca(2+) channels (CaV)...
July 2014: Cell Calcium
Arnaud L Lalive, Michaelanne B Munoz, Camilla Bellone, Paul A Slesinger, Christian Lüscher, Kelly R Tan
G-protein-coupled inwardly rectifying potassium (GIRK) channels contribute to the resting membrane potential of many neurons, including dopamine (DA) neurons in the ventral tegmental area (VTA). VTA DA neurons are bistable, firing in two modes: one characterized by bursts of action potentials, the other by tonic firing at a lower frequency. Here we provide evidence that these firing modes drive bidirectional plasticity of GIRK channel-mediated currents. In acute midbrain slices of mice, we observed that in vitro burst activation of VTA DA neurons potentiated GIRK currents whereas tonic firing depressed these currents...
April 9, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Nancy Stanslowsky, Alexandra Haase, Ulrich Martin, Maximilian Naujock, Andreas Leffler, Reinhard Dengler, Florian Wegner
INTRODUCTION: Human induced pluripotent stem cells (hiPSCs) offer great promise for regenerative therapies or in vitro modelling of neurodegenerative disorders like Parkinson's disease. Currently, widely used cell sources for the generation of hiPSCs are somatic cells obtained from aged individuals. However, a critical issue concerning the potential clinical use of these iPSCs is mutations that accumulate over lifetime and are transferred onto iPSCs during reprogramming which may influence the functionality of cells differentiated from them...
2014: Stem Cell Research & Therapy
Hongzhu Li, Can Wei, Jun Gao, Shuzhi Bai, Hongxia Li, Yajun Zhao, Hong Li, Liping Han, Ye Tian, Guangdong Yang, Rui Wang, Lingyun Wu, Changqing Xu
The physiological and pathological roles of dopamine D2 receptors (DR2) in the regulation of cardiovacular functions have been recognized. DR2 activation protects hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury and apoptosis, and ischemic post-conditioning (PC) plays a critical role in cardioprotection as well; however the involvement of the DR2 activation in the PC-induced cardioprotection is unknown. In the present study, we found that the H/R increased the expressions of DR2 mRNA and protein in cardiomyocytes, which were significantly enhanced by PC...
April 15, 2014: Experimental Cell Research
Neeta D Grover, Ramachandra P Limaye, Dilip V Gokhale, Tatyasaheb R Patil
The limitations of currently available therapies in addressing the non motor symptoms of Parkinson's disease (PD) have egged on the search for newer options. Zonisamide has been in use for epilepsy and it was serendipitously found to improve the symptoms of PD in a patient who had both epilepsy and PD. Thereafter, various trials were designed to assess the use of zonisamide in PD. The present article investigates the evidence for use of zonisamide in PD from the various clinical trials that were designed to address this issue...
November 2013: Indian Journal of Pharmacology
Michael H Silber
PURPOSE OF REVIEW: This article reviews the sleep-related movement disorders, including restless legs syndrome (RLS; Willis-Ekbom disease), periodic limb movement disorder, rhythmic movement disorders, sleep-related bruxism, and sleep-related leg cramps. RECENT FINDINGS: The prevalence of clinically significant RLS is 1.5% to 3.0%. The pathophysiology of RLS may involve abnormal iron transport across the blood-brain barrier and down-regulation of putaminal D2 receptors...
February 2013: Continuum: Lifelong Learning in Neurology
Wanhong Zuo, Lixin Chen, Liwei Wang, Jiang-Hong Ye
Cocaine administration can be both rewarding and aversive. While much effort has gone to investigating the rewarding effect, the mechanisms underlying cocaine-induced aversion remain murky. There is increasing evidence that the lateral habenula (LHb), a small epithalamic structure, plays a critical role in the aversive responses of many addictive drugs including cocaine. However, the effects of cocaine on LHb neurons are not well explored. Here we show that, in acute brain slices from rats, cocaine depolarized LHb neurons and accelerated their spontaneous firing...
July 2013: Neuropharmacology
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