Research Topics
| Robert KassSummaryAffiliation: Columbia University Country: USA Publications
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Detail Information
Publications
TEA(+)-sensitive KCNQ1 constructs reveal pore-independent access to KCNE1 in assembled I(Ks) channelsJ Kurokawa
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
J Gen Physiol 117:43-52. 2001....
Sodium channel inactivation in heart: a novel role of the carboxy-terminal domainRobert S Kass
Department of Pharmacology, Columbia University, New York, New York 10032, USA
J Cardiovasc Electrophysiol 17:S21-S25. 2006..Disruption of this interaction leads to persistent sodium channel current, action potential prolongation, and elevated risk of cardiac arrhythmia...- The channelopathies: novel insights into molecular and genetic mechanisms of human diseaseRobert S Kass
Department of Pharmacology, Columbia University Medical Center, New York, New York 10032, USA
J Clin Invest 115:1986-9. 2005..This series of reviews examines the roles of ion channels in health and disease... - Leucine/isoleucine zipper coordination of ion channel macromolecular signaling complexes in the heart. Roles in inherited arrhythmiasR S Kass
Department of Pharmacology Division of Cardiology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA
Trends Cardiovasc Med 13:52-6. 2003..Disruption of local signaling by disease-associated LIZ mutations unbalances the physiologic response to SNS stimulation and increases the risk of arrhythmia in mutation carriers... - Pharmacogenomics in the treatment of epilepsyColleen E Clancy
Department of Pharmacology, Columbia University, College of Physicians and Surgeons, 630 W 168th Street, New York, NY 10032, USA
Pharmacogenomics 4:747-51. 2003..The investigation of relationships between genotype and patient responses to drug treatment is termed pharmacogenomics... - Long QT syndrome: novel insights into the mechanisms of cardiac arrhythmiasRobert S Kass
Department of Pharmacology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, P and S 7 401, New York, New York 10032, USA
J Clin Invest 112:810-5. 2003..Discovery and analysis of gene mutations associated with variants of this disorder have provided novel insight into mechanisms of cardiac arrhythmia and have raised the possibility of mutation-specific therapeutic intervention... - Biophysical properties of slow potassium channels in human embryonic stem cell derived cardiomyocytes implicate subunit stoichiometryKai Wang
Department of Pharmacology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY 10032, USA
J Physiol 589:6093-104. 2011..This establishes a new baseline for I(Ks) channel properties in myocytes derived from pluripotent stem cells and will guide future studies in patient-specific hiPSCs... - A novel LQT-3 mutation disrupts an inactivation gate complex with distinct rate-dependent phenotypic consequencesJohn R Bankston
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
Channels (Austin) 1:273-80. 2007.... - Non-equilibrium gating in cardiac Na+ channels: an original mechanism of arrhythmiaColleen E Clancy
Department of Pharmacology, Columbia University College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032, USA
Circulation 107:2233-7. 2003.... - Autonomic control of cardiac action potentials: role of potassium channel kinetics in response to sympathetic stimulationCecile Terrenoire
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
Circ Res 96:e25-34. 2005..The full text of this article is available online at http://circres.ahajournals.org... - K+ channel structure-activity relationships and mechanisms of drug-induced QT prolongationColleen E Clancy
Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
Annu Rev Pharmacol Toxicol 43:441-61. 2003..Drug-induced disruption of cellular repolarization underlies electrocardiographic abnormalities that are diagnostic indicators of arrhythmia susceptibility... - Role of sodium channels in propagation in heart muscle: how subtle genetic alterations result in major arrhythmic disordersCecile Terrenoire
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
J Cardiovasc Electrophysiol 18:900-5. 2007..The improved understanding of the mechanisms leading to these cardiac arrhythmic events represents a first step in the development of therapeutic treatments... - Molecular basis of ranolazine block of LQT-3 mutant sodium channels: evidence for site of actionSandra Fredj
Department of Pharmacology, Columbia University Medical Center, New York, NY 10032, USA
Br J Pharmacol 148:16-24. 2006.... - Theoretical investigation of the neuronal Na+ channel SCN1A: abnormal gating and epilepsyColleen E Clancy
Department of Pharmacology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
Biophys J 86:2606-14. 2004..This work represents a first step in developing a comprehensive theoretical model to investigate the molecular mechanisms underlying runaway excitation that cause epilepsy... - Defective cardiac ion channels: from mutations to clinical syndromesColleen E Clancy
Department of Pharmacology, Columbia University, 630 West 168th Street, New York, New York 10032, USA
J Clin Invest 110:1075-7. 2002 - Modulation of cardiac sodium channel gating by protein kinase A can be altered by disease-linked mutationMichihiro Tateyama
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, 630 W 168th Street, New York, NY 10032, USA
J Biol Chem 278:46718-26. 2003.... - A carboxyl-terminal hydrophobic interface is critical to sodium channel function. Relevance to inherited disordersIan W Glaaser
Department of Pharmacology, Columbia University, New York, New York 10032, USA
J Biol Chem 281:24015-23. 2006..We thus demonstrate a novel role of the sodium channel COOH terminus structure in the control of channel inactivation and in pathologies caused by inherited mutations that disrupt it... - Insights into the molecular mechanisms of bradycardia-triggered arrhythmias in long QT-3 syndromeColleen E Clancy
Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
J Clin Invest 110:1251-62. 2002..These results link mutation-induced changes in Na+ channel gating mode transitions to heart rate-dependent changes in cellular electrical activity underlying a key LQT-3 clinical phenotype... - Channel openings are necessary but not sufficient for use-dependent block of cardiac Na(+) channels by flecainide: evidence from the analysis of disease-linked mutationsHuajun Liu
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
J Gen Physiol 120:39-51. 2002..Analysis of flecainide block of mutant channels linked to these rare disorders has provided novel insight into the molecular determinants of drug action... - Inherited and acquired vulnerability to ventricular arrhythmias: cardiac Na+ and K+ channelsColleen E Clancy
Department of Physiology and Biophysics, Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York 10021, USA
Physiol Rev 85:33-47. 2005..Improving understanding of abnormalities may provide a basis for the development of therapeutic approaches... - Stabilization of cardiac ryanodine receptor prevents intracellular calcium leak and arrhythmiasStephan E Lehnart
Department of Physiology, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University, New York, NY 10032, USA
Proc Natl Acad Sci U S A 103:7906-10. 2006..Our data suggest that calstabin-2 deficiency is as a critical mediator of triggers that initiate cardiac arrhythmias... - Mutation of an A-kinase-anchoring protein causes long-QT syndromeLei Chen
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
Proc Natl Acad Sci U S A 104:20990-5. 2007..Thus, we have demonstrated a link between genetic perturbations in AKAP and human disease in general and AKAP9 and LQTS in particular... - Leaky Ca2+ release channel/ryanodine receptor 2 causes seizures and sudden cardiac death in miceStephan E Lehnart
Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
J Clin Invest 118:2230-45. 2008..Based on these data, we propose that CPVT is a combined neurocardiac disorder in which leaky RyR2 channels in the brain cause epilepsy, and the same leaky channels in the heart cause exercise-induced sudden cardiac death... - Molecular determinants of local anesthetic action of beta-blocking drugs: Implications for therapeutic management of long QT syndrome variant 3John R Bankston
Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
J Mol Cell Cardiol 48:246-53. 2010..Furthermore our results indicate that this activity, like that of local anesthetic drugs, differs both with drug structure and the biophysical changes in Na(+) channel function caused by specific LQT-3 mutations... - Altered Na+ channels promote pause-induced spontaneous diastolic activity in long QT syndrome type 3 myocytesSandra Fredj
Department of Pharmacology, Columbia University Medical Center, New York, NY 10032, USA
Circ Res 99:1225-32. 2006.... - Requirement of a macromolecular signaling complex for beta adrenergic receptor modulation of the KCNQ1-KCNE1 potassium channelSteven O Marx
Department of Pharmacology, Center for Molecular Cardiology, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
Science 295:496-9. 2002..Yotiao binds to hKCNQ1 by a leucine zipper motif, which is disrupted by an LQTS mutation (hKCNQ1-G589D). Identification of the hKCNQ1 macromolecular complex provides a mechanism for SNS modulation of cardiac APD through IKS... - A novel SCN5A mutation associated with long QT-3: altered inactivation kinetics and channel dysfunctionIlaria Rivolta
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
Physiol Genomics 10:191-7. 2002..The effect of these alterations in channel gating results in an increase in window current that may act to disrupt cardiac repolarization... - Mechanisms of genetic arrhythmias: from DNA to ECGIan W Glaaser
Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
Prog Cardiovasc Dis 46:259-70. 2003..Additionally, phenotypically opposite and overlapping cardiac arrhythmogenic syndromes can even stem from the same mutation. Accordingly, the relationship between genetic mutations and clinical syndromes is becoming increasingly complex... - The Na+ channel inactivation gate is a molecular complex: a novel role of the COOH-terminal domainHoward K Motoike
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
J Gen Physiol 123:155-65. 2004.... - Adrenergic regulation of a key cardiac potassium channel can contribute to atrial fibrillation: evidence from an I Ks transgenic mouseKevin J Sampson
Department of Pharmacology, Columbia University Medical Center, 630 W 168th St, New York, NY 10032, USA
J Physiol 586:627-37. 2008.... - A novel and lethal de novo LQT-3 mutation in a newborn with distinct molecular pharmacology and therapeutic responseJohn R Bankston
Department of Pharmacology, College of Physicians and Surgeons, Columbia University Medical Center, New York, New York, United States of America
PLoS ONE 2:e1258. 2007.... - Electrophysiological consequences of human IKs channel expression in adult murine heartChristine Chiello Tracy
Department of Pharmacology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA
Am J Physiol Heart Circ Physiol 284:H168-75. 2003..I(Ks) channels impart beta-adrenergic sensitivity to the ventricles and may be responsible for ventricular tachyarrhythmias... - Common molecular determinants of flecainide and lidocaine block of heart Na+ channels: evidence from experiments with neutral and quaternary flecainide analoguesHuajun Liu
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
J Gen Physiol 121:199-214. 2003..The data also suggest that the two drugs share a common receptor but, consistent with the modulated receptor hypothesis, reach this receptor by distinct routes dictated by the degree of ionization of the drug molecules... - Phosphorylation of the A-kinase-anchoring protein Yotiao contributes to protein kinase A regulation of a heart potassium channelLei Chen
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
J Biol Chem 280:31347-52. 2005..These results suggest, for the first time, a critical role for the PKA phosphorylation of an AKAP in the functional regulation of an ion channel protein and postphosphorylation allosteric modulation of the I(Ks) channel by Yotiao... - Sodium channel inactivation goes with the flowRobert S Kass
Department of Pharmacology, Columbia University, New York, NY 10027, USA
J Gen Physiol 124:7-8. 2004 - Regulatory actions of the A-kinase anchoring protein Yotiao on a heart potassium channel downstream of PKA phosphorylationJunko Kurokawa
Department of Pharmacology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA
Proc Natl Acad Sci U S A 101:16374-8. 2004..These data reveal previously undescribed actions of Yotiao that occur subsequent to channel phosphorylation and provide evidence that this adaptor protein also may serve as an effector in regulating this important ion channel... - Location, location, regulation: a novel role for β-spectrin in the heartKevin J Sampson
Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York, USA
J Clin Invest 120:3434-7. 2010.... - Requirement of subunit expression for cAMP-mediated regulation of a heart potassium channelJunko Kurokawa
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, New York, NY 10032, USA
Proc Natl Acad Sci U S A 100:2122-7. 2003..Transduction of protein phosphorylation into physiologically necessary channel function represents a previously uncharacterized role for the KCNE1 auxiliary subunit, which can be disrupted in LQT-5... - The cardiac IKs potassium channel macromolecular complex includes the phosphodiesterase PDE4D3Cecile Terrenoire
Department of Pharmacology, Columbia University Medical Center, New York, New York 10032, USA
J Biol Chem 284:9140-6. 2009..We conclude that PDE4D3, like protein kinase A and protein phosphatase 1, is recruited to the I(Ks) channel via AKAP-9 and contributes to its critical regulation by cAMP... - Secondary structure of the human cardiac Na+ channel C terminus: evidence for a role of helical structures in modulation of channel inactivationJoseph W Cormier
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
J Biol Chem 277:9233-41. 2002..025% S1885stop (n = 7) versus 0.0028% wild type (n = 9), p < 0.005). These results suggest that the charged structured region of the SCN5A C terminus plays a major role in channel inactivation, stabilizing the inactivated state... - Molecular mechanisms of adrenergic stimulation in the heartKevin J Sampson
Department of Pharmacology, Columbia University, New York, New York 10032, USA
Heart Rhythm 7:1151-3. 2010..This article briefly reviews the major components of the beta-adrenergic pathway in the heart and discusses the direction of current and future research... - Overexpression of beta2-adrenergic receptors cAMP-dependent protein kinase phosphorylates and modulates slow delayed rectifier potassium channels expressed in murine heart: evidence for receptor/channel co-localizationKeith W Dilly
Department of Pharmacology, Center for Molecular Cardiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
J Biol Chem 279:40778-87. 2004..These data indicate intimate association of KCNQ1 and beta2-ARs and that beta2-AR signaling can modulate the function of IKs channels under conditions of increased beta2-AR expression, even in the absence of exogenous beta-AR agonist... - Calmodulin mediates Ca2+ sensitivity of sodium channelsJames Kim
Department of Pharmacology, Division of Cardiology, Columbia University, New York, New York 10032, USA
J Biol Chem 279:45004-12. 2004..Together, these data offer new biochemical evidence for Ca2+/CaM modulation of Na+ channel function... - Dual roles of the A kinase-anchoring protein Yotiao in the modulation of a cardiac potassium channel: a passive adaptor versus an active regulatorLei Chen
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, 630 W. 168th St, New York, NY 10032, USA
Eur J Cell Biol 85:623-6. 2006..It acts not only as an adaptor protein to coordinate enzymatic reactions but also as an active regulator that directly affects channel function... - A novel mutation L619F in the cardiac Na+ channel SCN5A associated with long-QT syndrome (LQT3): a role for the I-II linker in inactivation gatingXander H T Wehrens
Department of Cardiology, Cardiovascular Research Institute Maastricht, The Netherlands
Hum Mutat 21:552. 2003..Moreover, the defective inactivation imposed by the L619F mutation implies a role for the I-II linker in the Na(+) channel inactivation process... - Cardiac voltage-gated sodium channel Nav1.5 is regulated by Nedd4-2 mediated ubiquitinationMiguel X van Bemmelen
Department of Pharmacology and Toxicology, University of Lausanne, Switzerland
Circ Res 95:284-91. 2004..5. These results demonstrate that Na(v)1.5 can be ubiquitinated in heart tissues and that the ubiquitin-protein ligase Nedd4-2 acts on Na(v)1.5 by decreasing the channel density at the cell surface... - Regulation of the voltage-gated cardiac sodium channel Nav1.5 by interacting proteinsHugues Abriel
Department of Pharmacology and Toxicology, Service of Cardiology, University of Lausanne, Bugnon, 27, 1005 Lausanne, Switzerland
Trends Cardiovasc Med 15:35-40. 2005..5: ankyrin proteins, fibroblast growth factor homologous factor 1B, calmodulin, Nedd4-like ubiquitin-protein ligases, and syntrophin proteins... - Novel pore mutation in SCN5A manifests as a spectrum of phenotypes ranging from atrial flutter, conduction disease, and Brugada syndrome to sudden cardiac deathTom Rossenbacker
Center for Transgene Technology and Gene Therapy, Flanders Interuniversitary Institute for Biotechnology, KULeuven, Belgium
Heart Rhythm 1:610-5. 2004..Differentiating between electrophysiologic entities (Brugada syndrome-isolated cardiac conduction defect) is more challenging. Recognition of factors modifying the clinical presentation may be important for clinical decision making... - Clinical, genetic, and electrophysiologic characteristics of a new PAS-domain HERG mutation (M124R) causing Long QT syndromeLiat Shushi
Department of Genetics, The Life Sciences Institute, The Hebrew University, Jerusalem, Israel
Ann Noninvasive Electrocardiol 10:334-41. 2005..This mutation markedly decreased the tail-current density and accelerated the deactivation kinetics of the HERG channel in transfected CHO cells... - Variable expression of long QT syndrome among gene carriers from families with five different HERG mutationsJesaia Benhorin
Department of Cardiology, Bikur Cholim Hospital, Jerusalem, Israel
Ann Noninvasive Electrocardiol 7:40-6. 2002..These findings highlight the complexity of the clinical phenotype in this Mendelian dominant disorder and suggest that one or more modifier genes contribute to the variable expression of this syndrome... - Long QT syndrome: from channels to cardiac arrhythmiasArthur J Moss
Heart Research Follow Up Program, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
J Clin Invest 115:2018-24. 2005.... - Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmiaIgor Splawski
Department of Cardiology, Children s Hospital, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA
Science 297:1333-6. 2002..However, Y1102 may be a useful molecular marker for the prediction of arrhythmia susceptibility in the context of additional acquired risk factors such as the use of certain medications... - Molecular physiology of cardiac repolarizationJeanne M Nerbonne
Dept of Molecular Biology and Pharmacology, Washington University Medical School, 660 South Euclid Avenue, St Louis, MO 63110, USA
Physiol Rev 85:1205-53. 2005.... - Proposed diagnostic criteria for the Brugada syndrome: consensus reportArthur A M Wilde
Experimental and Molecular Cardiology Group, Academic Medical Center, Amsterdam, and the Interuniversity Cardiology Institute, The Netherlands
Circulation 106:2514-9. 2002 - Mutation of sodium channel SCN3A in a patient with cryptogenic pediatric partial epilepsyKatherine D Holland
Division of Neurology, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
Neurosci Lett 433:65-70. 2008..This observation of a potentially pathogenic mutation of SCN3A (Nav1.3) indicates that this gene should be further evaluated for its contribution to childhood epilepsy... - Fading sodium channels in failing heartsJohn R Bankston
Circ Res 101:1073-4. 2007 - A-kinase anchoring proteins: different partners, different danceLei Chen
Nat Cell Biol 7:1050-1. 2005 - Regulation of endocytic recycling of KCNQ1/KCNE1 potassium channelsGuiscard Seebohm
Department of Physiology I, University of Tuebingen, Gmelinstrasse 5, D 72076 Tuebingen, Germany
Circ Res 100:686-92. 2007....
Research Grants
- Molecular Determinants of K+ Channel Regulation in HeartRobert Kass; Fiscal Year: 2004..abstract_text> ..
- MOLECULAR PHARMACOLOGY OF AN INHERITED HEART DISEASERobert Kass; Fiscal Year: 2006..abstract_text> ..
- TRAINING PROGRAM IN PHARMACOLOGICAL SCIENCESRobert Kass; Fiscal Year: 2006..abstract_text> ..
- MOLECULAR PHARMACOLOGY OF AN INHERITED HEART DISEASERobert Kass; Fiscal Year: 2007....
- Molecular Determinants of K+ Channel Regulation in HeartRobert Kass; Fiscal Year: 2009..The results of these investigations will provide novel insight into and understanding of the molecular interactions that underlie this fundamental and essential cardiac response. ..
- MOLECULAR PHARMACOLOGY OF AN INHERITED HEART DISEASERobert S Kass; Fiscal Year: 2010....
- K+ CHANNELS IN NORMAL AND GENETICALLY ALTERED HEARTRobert Kass; Fiscal Year: 2000..The results of these studies should provide the most detailed description to date of the molecular and genetic properties of IKs and its relevance to human cardiovascular pharmacology and disease. ..
- MOLECULAR PHARMACOLOGY OF AN INHERITED HEART DISEASERobert Kass; Fiscal Year: 2001..non-carriers of the LQT-1 and LQT-3 gene mutations to optimize experimental design and therapeutic approaches. ..
- CHARGED DIHYDROPYRIDINES--PROBES OF HEART CA++ CHANNELSRobert Kass; Fiscal Year: 2001....
- Molecular Determinants of K+ Channel Regulation in HeartRobert S Kass; Fiscal Year: 2010..Thus the goal of this work is to define new molecular motifs that are responsible for, and can be targeted to treat, specific congenital cardiac arrhythmias. ..