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
2003 Aug 01;3682:119-26. doi: 10.1007/s00210-003-0772-x.
Show Gene links
Show Anatomy links
Human beta(3)-adrenoreceptors couple to KvLQT1/MinK potassium channels in Xenopus oocytes via protein kinase C phosphorylation of the KvLQT1 protein.
Kathöfer S
,
Röckl K
,
Zhang W
,
Thomas D
,
Katus H
,
Kiehn J
,
Kreye V
,
Schoels W
,
Karle C
.
???displayArticle.abstract???
Modulation of the slow component of the delayed rectifier potassium current (IKs) in heart critically affects cardiac arrhythmogenesis. Its current amplitude is regulated by the sympathetic nervous system. However, the signal transduction from the beta-adrenergic system to the KvLQT1/MinK (KCNQ1/KCNE1) potassium channel, which is the molecular correlate of the IKs current in human cardiomyocytes, is not sufficiently understood. In the human heart, three subtypes of beta-adrenergic receptors (beta(1-3)-ARs) have been identified. Only beta(1)- and beta(3)-ARs have been shown so far to be involved in the regulation of IKs. Special interest has been paid to the regulation of IKs by the beta(3)-AR because of its potential importance in congestive heart failure. In heart failure beta(1)-ARs are known to be down regulated while the density of beta(3)-ARs is increased. Unfortunately, studies on the modulation of IKs by beta(3)-AR revealed conflicting results. We investigated the functional role of protein kinase C (PKC) in the signal transduction cascade between beta3-adrenergic receptors and IKs by expressing heterologously its molecular components, the KvLQT1/MinK potassium channel, together with human beta(3)-AR in Xenopus oocytes. Membrane currents were measured with the double electrode voltage-clamp technique. Using activators and inhibitors of PKC we demonstrated that PKC is involved in this regulatory process. Experiments in which the putative C-terminal PKC-phosphorylation sites in the KvLQT1 protein were destroyed by site directed mutagenesis reduced the isoproterenol-induced current to 27+/-3,5% compared to control. These results indicate that the amplitude of KvLQT1/MinK current is mainly increased by PKC activation. Our results suggest that the regulation of the KvLQT1/MinK potassium channel via beta(3)-AR is substantially mediated by PKC phosphorylation of the KvLQT1 protein at its four C-terminal PKC phosphorylation sites.
Barhanin,
K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current.
1996, Pubmed,
Xenbase
Barhanin,
K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current.
1996,
Pubmed
,
Xenbase
Bosch,
beta3-Adrenergic regulation of an ion channel in the heart-inhibition of the slow delayed rectifier potassium current I(Ks) in guinea pig ventricular myocytes.
2002,
Pubmed
,
Xenbase
Brodde,
Adrenergic and muscarinic receptors in the human heart.
1999,
Pubmed
Busch,
Effects of [Ca2+]i and temperature on minK channels expressed in Xenopus oocytes.
1993,
Pubmed
,
Xenbase
Cheng,
Upregulation of functional beta(3)-adrenergic receptor in the failing canine myocardium.
2001,
Pubmed
Clancy,
K+ channel structure-activity relationships and mechanisms of drug-induced QT prolongation.
2003,
Pubmed
Conrath,
beta3-Adrenoceptors in the heart.
2002,
Pubmed
Duchatelle-Gourdon,
Modulation of the delayed rectifier potassium current in frog cardiomyocytes by beta-adrenergic agonists and magnesium.
1989,
Pubmed
Gauthier,
The negative inotropic effect of beta3-adrenoceptor stimulation is mediated by activation of a nitric oxide synthase pathway in human ventricle.
1998,
Pubmed
Gauthier,
Functional beta3-adrenoceptor in the human heart.
1996,
Pubmed
Gauthier,
Beta3-adrenoceptors in the cardiovascular system.
2000,
Pubmed
Haeffner,
Ca2+ and partly GTP gamma S-dependent particulate phospholipase C hydrolyzing phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate is inhibited by diacyl(acyl-acetyl) glycerols.
1992,
Pubmed
Herbert,
Chelerythrine is a potent and specific inhibitor of protein kinase C.
1990,
Pubmed
Hjalmarson,
Effects of beta blockade on sudden cardiac death during acute myocardial infarction and the postinfarction period.
1997,
Pubmed
Iost,
Delayed rectifier potassium current in undiseased human ventricular myocytes.
1998,
Pubmed
Kaczmarek,
Properties and regulation of the minK potassium channel protein.
1997,
Pubmed
,
Xenbase
Kass,
The roles of ion channels in an inherited heart disease: molecular genetics of the long QT syndrome.
1996,
Pubmed
Kathöfer,
Functional coupling of human beta 3-adrenoreceptors to the KvLQT1/MinK potassium channel.
2000,
Pubmed
,
Xenbase
Kaumann,
Modulation of human cardiac function through 4 beta-adrenoceptor populations.
1997,
Pubmed
Konkar,
beta1-adrenergic receptors mediate beta3-adrenergic-independent effects of CGP 12177 in brown adipose tissue.
2000,
Pubmed
Kurokawa,
Requirement of subunit expression for cAMP-mediated regulation of a heart potassium channel.
2003,
Pubmed
Lafontan,
Differential recruitment and differential regulation by physiological amines of fat cell beta-1, beta-2 and beta-3 adrenergic receptors expressed in native fat cells and in transfected cell lines.
1994,
Pubmed
Li,
Transmembrane ICa contributes to rate-dependent changes of action potentials in human ventricular myocytes.
1999,
Pubmed
Lo,
Independent and exclusive modulation of cardiac delayed rectifying K+ current by protein kinase C and protein kinase A.
1998,
Pubmed
,
Xenbase
Lowe,
Action potential shortening through the putative beta4-adrenoceptor in ferret ventricle: comparison with beta1- and beta2-adrenoceptor-mediated effects.
1998,
Pubmed
Marx,
Requirement of a macromolecular signaling complex for beta adrenergic receptor modulation of the KCNQ1-KCNE1 potassium channel.
2002,
Pubmed
Moniotte,
Upregulation of beta(3)-adrenoceptors and altered contractile response to inotropic amines in human failing myocardium.
2001,
Pubmed
Nattel,
Acquired delayed rectifier channelopathies: how heart disease and antiarrhythmic drugs mimic potentially-lethal congenital cardiac disorders.
2000,
Pubmed
Packer,
Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study.
2002,
Pubmed
Roden,
Multiple mechanisms in the long-QT syndrome. Current knowledge, gaps, and future directions. The SADS Foundation Task Force on LQTS.
1996,
Pubmed
Sanguinetti,
Isoproterenol antagonizes prolongation of refractory period by the class III antiarrhythmic agent E-4031 in guinea pig myocytes. Mechanism of action.
1991,
Pubmed
Sanguinetti,
Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel.
1996,
Pubmed
,
Xenbase
Schnabel,
Binding properties of beta-blockers at recombinant beta1-, beta2-, and beta3-adrenoceptors.
2000,
Pubmed
Splawski,
Mutations in the hminK gene cause long QT syndrome and suppress IKs function.
1997,
Pubmed
,
Xenbase
Strosberg,
Function and regulation of the beta 3-adrenoceptor.
1996,
Pubmed
Strosberg,
Structure, function, and regulation of adrenergic receptors.
1993,
Pubmed
Toullec,
The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C.
1991,
Pubmed
Varnum,
The min K channel underlies the cardiac potassium current IKs and mediates species-specific responses to protein kinase C.
1993,
Pubmed
,
Xenbase
Veldkamp,
Is the slowly activating component of the delayed rectifier current, IKs' absent from undiseased human ventricular myocardium?
1998,
Pubmed
Walsh,
Beta-adrenergic modulation of cardiac ion channels. Differential temperature sensitivity of potassium and calcium currents.
1989,
Pubmed
Zeng,
Two components of the delayed rectifier K+ current in ventricular myocytes of the guinea pig type. Theoretical formulation and their role in repolarization.
1995,
Pubmed
