ArticleThe Journal of general physiology2000
Dominant-negative mutants identify a role for GIRK channels in D3 dopamine receptor-mediated regulation of spontaneous secretory activity.
Article in The Journal of general physiology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 45 citations in OpenAlex.
- HCN4 ion channel function is required for early events that regulate anatomical left-right patterning in a nodal and lefty asymmetric gene expression-independent manner.Biology open · 2017Article
- Coordinating heart morphogenesis: A novel role for hyperpolarization-activated cyclic nucleotide-gated (HCN) channels during cardiogenesis inCommunicative & integrative biology · 2017Article
- Striatal dopamine neurotransmission: regulation of release and uptake.Basal ganglia · 2016Article
- Alternatively Spliced Isoforms of KV10.1 Potassium Channels Modulate Channel Properties and Can Activate Cyclin-dependent Kinase in Xenopus Oocytes.The Journal of biological chemistry · 2015Article
- Bioelectric signaling regulates size in zebrafish fins.PLoS genetics · 2014Article
- Postsynaptic ERG potassium channels limit muscle excitability to allow distinct egg-laying behavior states in Caenorhabditis elegans.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Molecular characterization of individual D3 dopamine receptor-expressing cells isolated from multiple brain regions of a novel mouse model.Brain structure & function · 2012Article
- Identification and characterization of a novel class of atypical dopamine receptor agonists.Pharmaceutical research · 2012Article
- Regulation of striatal dopamine release by presynaptic auto- and heteroreceptors.Basal ganglia · 2012Article
- Control of firing patterns through modulation of axon initial segment T-type calcium channels.The Journal of physiology · 2012Article
- Do caveolae have a role in the fidelity and dynamics of receptor activation of G-protein-gated inwardly rectifying potassium channels?The Journal of biological chemistry · 2010Article
- Dysregulation of dopamine-dependent mechanisms as a determinant of hypertension: studies in dopamine receptor knockout mice.American journal of physiology. Heart and circulatory physiology · 2008Review
- p75 neurotrophin receptor mediates neuronal cell death by activating GIRK channels through phosphatidylinositol 4,5-bisphosphate.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2008Article
- D3 dopamine autoreceptors do not activate G-protein-gated inwardly rectifying potassium channel currents in substantia nigra dopamine neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2003Article
- Evaluation of D2 and D3 dopamine receptor selective compounds on L-dopa-dependent abnormal involuntary movements in rats.NeuropharmacologyArticle
- Evaluation of the D3 dopamine receptor selective agonist/partial agonist PG01042 on L-dopa dependent animal involuntary movements in rats.NeuropharmacologyArticle
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2 authors at 1 institution in 1 country.
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Abstract
The human D3 dopamine receptor can activate G-protein-coupled inward rectifier potassium channels (GIRKs), inhibit P/Q-type calcium channels, and inhibit spontaneous secretory activity in AtT-20 neuroendocrine cells (Kuzhikandathil, E.V., W. Yu, and G.S. Oxford. 1998. Mol. Cell. Neurosci. 12:390-402; Kuzhikandathil, E.V., and G.S. Oxford. 1999. J. Neurosci. 19:1698-1707). In this study, we evaluate the role of GIRKs in the D3 receptor-mediated inhibition of secretory activity in AtT-20 cells. The absence of selective blockers for GIRKs has precluded a direct test of the hypothesis that they play an important role in inhibiting secretory activity. However, the tetrameric structure of these channels provides a means of disrupting endogenous GIRK function using a dominant negative approach. To develop a dominant-negative GIRK mutant, the K(+) selectivity amino acid sequence -GYG- in the putative pore domain of the human GIRK2 channels was mutated to -AAA-, -GLG-, or -GFG-. While the mutation of -GYG- to -GFG- did not affect channel function, both the -AAA- and -GLG- GIRK2 mutants were nonfunctional. This suggests that the aromatic ring of the tyrosine residue rather than its hydroxyl group is involved in maintaining the pore architecture of human GIRK2 channels. When expressed in AtT-20 cells, the nonfunctional AAA-GIRK2 and GLG-GIRK2 acted as effective dominant-negative mutants and significantly attenuated endogenous GIRK currents. Furthermore, these dominant-negative mutants interfered with the D3 receptor-mediated inhibition of secretion in AtT-20 cells, suggesting they are centrally involved in the signaling pathway of this secretory response. These results indicate that dominant-negative GIRK mutants are effective molecular tools to examine the role of GIRK channels in vivo.
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