Differential voltage-sensitivity of D2-like dopamine receptors

Sahlholm, Kristoffer; Marcellino, Daniel; Nilsson, Johanna; Fuxé, Kjell; Århem, Peter

doi:10.1016/j.bbrc.2008.07.052

Cited by 22 publications

(17 citation statements)

References 20 publications

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“…GFP+ Drd2/Pet1 neurons, but not mCherry+ Pet1- only neurons, demonstrated a voltage-dependent response to administration of 10 μM quinpirole: at low voltages, GFP+ neurons showed a positive inward (excitatory) current while at voltages greater than ~−65 mV they showed a positive outward (inhibitory) current (Figure 5F). The nature of the quinpirole-induced GFP+ neuron response suggests the activation of a G-protein coupled inwardly rectifying potassium channel (GIRK; (Lesage et al, 1994, Sahlholm et al, 2008)).…”

Section: Resultsmentioning

confidence: 99%

Identification of Serotonergic Neuronal Modules that Affect Aggressive Behavior

et al. 2016

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Summary Escalated aggression can have devastating societal consequences, yet underlying neurobiological mechanisms are poorly understood. Here we show significantly increased inter-male mouse aggression when neurotransmission is constitutively blocked from either of two subsets of serotonergic, Pet1+ neurons – one identified by dopamine receptor D1(Drd1a)::cre driven activity perinatally, the other by Drd2::cre from pre-adolescence onward. Blocking neurotransmission from other Pet1+ neuron subsets of similar size and/or overlapping anatomical domains had no effect on aggression compared to controls, suggesting subtype-specific serotonergic neuron influences on aggression. Using established and novel intersectional genetic tools, we further characterized these subtypes across multiple parameters, showing both overlapping and distinct features in axonal projection targets, gene expression, electrophysiological properties, and effects on non-aggressive behaviors. Notably, Drd2::cre-marked 5-HT neurons exhibited D2-dependent inhibitory responses to dopamine in slices, suggesting direct and specific interplay between inhibitory dopaminergic signaling and a serotonergic subpopulation. Thus, we identify specific serotonergic modules that shape aggression.

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Section: Resultsmentioning

confidence: 99%

Identification of Serotonergic Neuronal Modules that Affect Aggressive Behavior

et al. 2016

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“…Furthermore, dopamine regulates the activity of several voltage-gated ion channels and transcription factors, which in turn activate transcription of early and late genes that are essential for the long-lasting effects of dopamine on synaptic transmission. Very recent data also suggest that the D2-like receptors themselves are voltage-dependent, demonstrating that the membrane potential could influence the potency with which dopamine is able to activate the receptor [129,130]. These observations suggest a function for D2-like receptor in activity-dependent regulation of synaptic strength.…”

Section: Physiological Role Of the D4 Receptor In The Brainmentioning

confidence: 87%

The dopamine D4 receptor: biochemical and signalling properties

Rondou

Haegeman

Craenenbroeck

2010

Cell. Mol. Life Sci.

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Dopamine is an important neurotransmitter that regulates several key functions in the brain, such as motor output, motivation and reward, learning and memory, and endocrine regulation. Dopamine does not mediate fast synaptic transmission, but rather modulates it by triggering slow-acting effects through the activation of dopamine receptors, which belong to the G-protein-coupled receptor superfamily. Besides activating different effectors through G-protein coupling, dopamine receptors also signal through interaction with a variety of proteins, collectively termed dopamine receptor-interacting proteins. We focus on the dopamine D4 receptor, which contains an important polymorphism in its third intracellular loop. This polymorphism has been the subject of numerous studies investigating links with several brain disorders, such as attention-deficit hyperactivity disorder and schizophrenia. We provide an overview of the structure, signalling properties and regulation of dopamine D4 receptors, and briefly discuss their physiological and pathophysiological role in the brain.

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“…Agonist affinities and functional potencies at a number of GPCRs, including D 2 R, D 4 R, and muscarinic M 2 receptors (M 2 R; (Ben-Chaim et al, 2003;Sahlholm et al, 2008a), have been shown to be regulated by the membrane potential. Interestingly, DA potency in D 3 R-mediated GIRK activation was not significantly different between -80 and 0 mV, suggesting that this receptor might be insensitive to voltage (Sahlholm et al, 2008a). However, the influence of the membrane potential on agonist potency at the D 1 -like family of receptors remains unexplored.…”

Section: Introductionmentioning

confidence: 99%

“…Several previous experimental investigations of GPCR voltage-dependence have made use of two-electrode voltage-clamp in Xenopus oocytes heterologously expressing GPCRs and G protein-coupled inward-rectifying potassium (GIRK) channels. This has allowed for investigation of GPCR activity by measuring GIRK activation evoked by Ga i/o -coupled GPCRs (Ben-Chaim et al, 2003;Sahlholm et al, 2008a;Sahlholm et al, 2011;Sahlholm et al, 2012) and by Ga q -coupled GPCRs in the presence of a chimeric Ga q-i protein (Ohana et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Voltage-Dependent Dopamine Potency at D1-Like Dopamine Receptors

Ågren

Sahlholm

2020

Front. Pharmacol.

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In recent years, transmembrane voltage has been found to modify agonist potencies at several G protein-coupled receptors (GPCRs). Whereas the voltage sensitivities of the Ga i/o-coupled dopamine D 2-like receptors (D 2 R, D 3 R, D 4 R) have previously been investigated, the putative impact of transmembrane voltage on agonist potency at the mainly Ga s/olf-coupled dopamine D 1-like receptors (D 1 R, D 5 R) has hitherto not been reported. Here, we assayed the potency of dopamine in activating G protein-coupled inward rectifier potassium (GIRK) channels co-expressed with D 1 R and D 5 R in Xenopus oocytes, at-80 mV and at 0 mV. Furthermore, GIRK response deactivation rates upon dopamine washout were measured to estimate dopamine dissociation rate (k off) constants. Depolarization from-80 to 0 mV was found to reduce dopamine potency by about 7-fold at both D 1 R and D 5 R. This potency reduction was accompanied by an increase in estimated dopamine k off s at both receptors. While the GIRK response elicited via D 1 R was insensitive to pertussis toxin (PTX), the response evoked via D 5 R was reduced by 64% (-80 mV) and 71% (0 mV) in the presence of PTX. Injection of oocytes with Ga s antisense oligonucleotide inhibited the D 1 R-mediated response by 62% (-80 mV) and 76% (0 mV) and abolished the D 5 R response when combined with PTX. Our results suggest that depolarization decreases dopamine affinity at D 1 R and D 5 R. The voltagedependent affinities of dopamine at D 1 R and D 5 R may be relevant to the functions of these receptors in learning and memory.

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Differential voltage-sensitivity of D2-like dopamine receptors

Cited by 22 publications

References 20 publications

Identification of Serotonergic Neuronal Modules that Affect Aggressive Behavior

Identification of Serotonergic Neuronal Modules that Affect Aggressive Behavior

The dopamine D4 receptor: biochemical and signalling properties

Voltage-Dependent Dopamine Potency at D1-Like Dopamine Receptors

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