Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Naunyn Schmiedebergs Arch Pharmacol
2015 Jun 01;3886:653-61. doi: 10.1007/s00210-015-1109-2.
Show Gene links
Show Anatomy links
Cortisone and hydrocortisone inhibit human Kv1.3 activity in a non-genomic manner.
Yu J
,
Park MH
,
Choi SY
,
Jo SH
.
???displayArticle.abstract???
Glucocorticoids are hormones released in response to stress that are involved in various physiological processes including immune functions. One immune-modulating mechanism is achieved by the Kv1.3 voltage-dependent potassium channel, which is expressed highly in lymphocytes including effector memory T lymphocytes (TEM). Although glucocorticoids are known to inhibit Kv1.3 function, the detailed inhibitory mechanism is not yet fully understood. Here we studied the rapid non-genomic effects of cortisone and hydrocortisone on the human Kv1.3 channel expressed in Xenopus oocytes. Both cortisone and hydrocortisone reduced the amplitude of the Kv1.3 channel current in a concentration-dependent manner. Both cortisone and hydrocortisone rapidly and irreversibly inhibited Kv1.3 currents, eliminating the possibility of genomic regulation. Inhibition rate was stable relative to the degree of depolarization. Kinetically, cortisone altered the activating gate of Kv1.3 and hydrocortisone interacted with this channel in an open state. These results suggest that cortisone and hydrocortisone inhibit Kv1.3 currents via a non-genomic mechanism, providing a mechanism for the immunosuppressive effects of glucocorticoids.
Ader,
A structural link between inactivation and block of a K+ channel.
2008, Pubmed
Ader,
A structural link between inactivation and block of a K+ channel.
2008,
Pubmed
Anangi,
Recombinant expression of margatoxin and agitoxin-2 in Pichia pastoris: an efficient method for production of KV1.3 channel blockers.
2012,
Pubmed
Baker,
Evolution of hormone selectivity in glucocorticoid and mineralocorticoid receptors.
2013,
Pubmed
Beato,
Transcriptional regulation by steroid hormones.
1996,
Pubmed
Beeton,
Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases.
2006,
Pubmed
Bellavance,
The HPA - Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain.
2014,
Pubmed
Bergink,
Autoimmunity, inflammation, and psychosis: a search for peripheral markers.
2014,
Pubmed
Billing,
Proteomic profiling of rapid non-genomic and concomitant genomic effects of acute restraint stress on rat thymocytes.
2012,
Pubmed
Borski,
Nongenomic membrane actions of glucocorticoids in vertebrates.
2000,
Pubmed
Buttgereit,
Rapid glucocorticoid effects on immune cells.
2002,
Pubmed
Cahalan,
Ion channels in the immune system as targets for immunosuppression.
1997,
Pubmed
Chandy,
K+ channels as targets for specific immunomodulation.
2004,
Pubmed
Choi,
Inhibition of human ether-a-go-go-related gene K+ channel and IKr of guinea pig cardiomyocytes by antipsychotic drug trifluoperazine.
2005,
Pubmed
,
Xenbase
Decher,
Structural determinants of Kvbeta1.3-induced channel inactivation: a hairpin modulated by PIP2.
2008,
Pubmed
Evanson,
Nongenomic actions of adrenal steroids in the central nervous system.
2010,
Pubmed
Feske,
Gene regulation mediated by calcium signals in T lymphocytes.
2001,
Pubmed
Finsterwald,
Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies.
2014,
Pubmed
Fordyce,
Microglia Kv1.3 channels contribute to their ability to kill neurons.
2005,
Pubmed
Gutman,
International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels.
2005,
Pubmed
Hautz,
Targeting the Kv1.3 potassium channel for immunosuppression in vascularized composite allotransplantation - a pilot study.
2013,
Pubmed
Henke,
Regulation of the voltage gated K+ channel Kv1.3 by the ubiquitin ligase Nedd4-2 and the serum and glucocorticoid inducible kinase SGK1.
2004,
Pubmed
,
Xenbase
Hu,
Blockade of Kv1.3 potassium channels inhibits differentiation and granzyme B secretion of human CD8+ T effector memory lymphocytes.
2013,
Pubmed
Jiang,
Why do we need nongenomic glucocorticoid mechanisms?
2014,
Pubmed
Jo,
H(1) antihistamine drug promethazine directly blocks hERG K(+) channel.
2009,
Pubmed
,
Xenbase
Joëls,
Unraveling the time domains of corticosteroid hormone influences on brain activity: rapid, slow, and chronic modes.
2012,
Pubmed
Lagos,
Identification of novel 11β-HSD1 inhibitors by combined ligand- and structure-based virtual screening.
2014,
Pubmed
Lampert,
Effect of dexamethasone on voltage-gated K+ channels in Jurkat T-lymphocytes.
2003,
Pubmed
Liu,
Rapid inhibitory effect of corticosterone on histamine release from rat peritoneal mast cells.
2007,
Pubmed
Losel,
Nongenomic steroid action: controversies, questions, and answers.
2003,
Pubmed
Lösel,
Nongenomic actions of steroid hormones.
2003,
Pubmed
Náray-Fejes-Tóth,
Expression and characterization of a new species of 11 beta-hydroxysteroid dehydrogenase in Xenopus oocytes.
1993,
Pubmed
,
Xenbase
Pazirandeh,
Effects of altered glucocorticoid sensitivity in the T cell lineage on thymocyte and T cell homeostasis.
2002,
Pubmed
Pitzalis,
Regulation of leukocyte-endothelial interactions by glucocorticoids.
2002,
Pubmed
Rhen,
Antiinflammatory action of glucocorticoids--new mechanisms for old drugs.
2005,
Pubmed
Rivest,
How circulating cytokines trigger the neural circuits that control the hypothalamic-pituitary-adrenal axis.
2001,
Pubmed
Sarabdjitsingh,
Glucocorticoid pulsatility and rapid corticosteroid actions in the central stress response.
2012,
Pubmed
Stahn,
Genomic and nongenomic effects of glucocorticoids.
2008,
Pubmed
Swanson,
Cloning and expression of cDNA and genomic clones encoding three delayed rectifier potassium channels in rat brain.
1990,
Pubmed
,
Xenbase
Villalonga,
Immunomodulation of voltage-dependent K+ channels in macrophages: molecular and biophysical consequences.
2010,
Pubmed
Wulff,
The voltage-gated Kv1.3 K(+) channel in effector memory T cells as new target for MS.
2003,
Pubmed
Yang,
Glucocorticoids and vascular reactivity.
2004,
Pubmed
Zhou,
A novel strategy for development of glucocorticoids through non-genomic mechanism.
2011,
Pubmed
de Kloet,
From receptor balance to rational glucocorticoid therapy.
2014,
Pubmed