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Brain Res
2012 May 03;1452:1-9. doi: 10.1016/j.brainres.2012.02.070.
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Sigma-1 receptor alters the kinetics of Kv1.3 voltage gated potassium channels but not the sensitivity to receptor ligands.
Kinoshita M
,
Matsuoka Y
,
Suzuki T
,
Mirrielees J
,
Yang J
.
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Sigma1 receptors (Sigma1R) are intracellular chaperone proteins that bind psychotropic drugs and also clinically used drugs such as ketamine and haloperidol. Co-expression of the Sigma1R has been reported to enhance the sensitivity of several voltage-gated ion channels to Sigma1R ligands. Kv1.3 is the predominant voltage-gated potassium channel expressed in T lymphocytes with a documented role in immune activation. To gain a better understanding of Sigma1R modulation of Kv ion channels, we investigated the effects of Sigma1R co-expression on Kv1.3 physiology and pharmacology in ion channels expressed in Xenopus oocytes. We also explored the protein domains of Kv1.3 necessary for protein:protein interaction between Kv1.3 and Sigma1R through co-immunoprecipitation studies. Slowly inactivating outward-going currents consistent with Kv1.3 expression were elicited on step depolarizations. The current characterized by E(rev), V(1/2), and slope factor remained unchanged when co-expressed with Sigma1R. Analysis of inactivation time constant revealed a faster Kv1.3 current decay when co-expressed with Sigma1R. However the sensitivity to Sigma1R ligands remained unaltered when co-expressed with the Sigma1R in contrast to the previously reported modulation of ligand sensitivity in closely related Kv1.4 and Kv1.5 voltage gated potassium channels. Co-immunoprecipitation assays of various Kv1.3 truncation constructs indicated that the transmembrane domain of the Kv1.3 protein was responsible for the protein:protein interaction with the Sigma1R. Sigma1R likely interacts with different domains of Kv ion channel family proteins resulting in distinct modulation of different channels.
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Aydar,
The sigma receptor as a ligand-regulated auxiliary potassium channel subunit.
2002, Pubmed,
Xenbase
Aydar,
The sigma receptor as a ligand-regulated auxiliary potassium channel subunit.
2002,
Pubmed
,
Xenbase
Beeton,
Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases.
2006,
Pubmed
Beeton,
Selective blockade of T lymphocyte K(+) channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis.
2001,
Pubmed
Carr,
Immunoregulatory properties of (+)-pentazocine and sigma ligands.
1992,
Pubmed
Casellas,
Immunopharmacological profile of SR 31747: in vitro and in vivo studies on humoral and cellular responses.
1994,
Pubmed
Church,
Blockade by sigma site ligands of high voltage-activated Ca2+ channels in rat and mouse cultured hippocampal pyramidal neurones.
1995,
Pubmed
Cobos,
Pharmacology and therapeutic potential of sigma(1) receptor ligands.
2008,
Pubmed
Cook,
Two adaptor proteins differentially modulate the phosphorylation and biophysics of Kv1.3 ion channel by SRC kinase.
2002,
Pubmed
DeCoursey,
Voltage-dependent ion channels in T-lymphocytes.
1985,
Pubmed
Ganapathy,
Molecular and ligand-binding characterization of the sigma-receptor in the Jurkat human T lymphocyte cell line.
1999,
Pubmed
Hayashi,
Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival.
2007,
Pubmed
Johannessen,
Voltage-gated sodium channel modulation by sigma-receptors in cardiac myocytes and heterologous systems.
2009,
Pubmed
Kiss,
Contribution of the selectivity filter to inactivation in potassium channels.
1999,
Pubmed
Kupper,
Functional expression of GFP-tagged Kv1.3 and Kv1.4 channels in HEK 293 cells.
1998,
Pubmed
Leykin,
Short and long-term immunosuppressive effects of clozapine and haloperidol.
1997,
Pubmed
Liu,
Sigma-1 receptors modulate functional activity of rat splenocytes.
1995,
Pubmed
Loots,
Molecular coupling of S4 to a K(+) channel's slow inactivation gate.
2000,
Pubmed
McCann,
Sigma-1 and sigma-2 sites in rat brain: comparison of regional, ontogenetic, and subcellular patterns.
1994,
Pubmed
Ohta,
Ketamine inhibits maturation of bone marrow-derived dendritic cells and priming of the Th1-type immune response.
2009,
Pubmed
Panyi,
C-type inactivation of a voltage-gated K+ channel occurs by a cooperative mechanism.
1995,
Pubmed
Panyi,
Ion channels and lymphocyte activation.
2004,
Pubmed
Rofael,
Immunomodulation by cocaine and ketamine in postnatal rats.
2003,
Pubmed
Spencer,
Purification, visualization, and biophysical characterization of Kv1.3 tetramers.
1997,
Pubmed
Su,
The sigma-1 receptor chaperone as an inter-organelle signaling modulator.
2010,
Pubmed
Tchedre,
Sigma-1 receptor regulation of voltage-gated calcium channels involves a direct interaction.
2008,
Pubmed
Veh,
Immunohistochemical localization of five members of the Kv1 channel subunits: contrasting subcellular locations and neuron-specific co-localizations in rat brain.
1995,
Pubmed
Wilke,
K+ channel modulation in rodent neurohypophysial nerve terminals by sigma receptors and not by dopamine receptors.
1999,
Pubmed
Wu,
Role of sigma-1 receptor C-terminal segment in inositol 1,4,5-trisphosphate receptor activation: constitutive enhancement of calcium signaling in MCF-7 tumor cells.
2008,
Pubmed
Yamada,
Propofol acts at the sigma-1 receptor and inhibits pentazocine-induced c-Fos expression in the mouse posterior cingulate and retrosplenial cortices.
2006,
Pubmed
Yao,
Molecular mechanisms involving sigma receptor-mediated induction of MCP-1: implication for increased monocyte transmigration.
2010,
Pubmed
Zhang,
Sigma receptors inhibit high-voltage-activated calcium channels in rat sympathetic and parasympathetic neurons.
2002,
Pubmed
Zhu,
IL-10 mediates sigma 1 receptor-dependent suppression of antitumor immunity.
2003,
Pubmed
