Research Topics
| Jonathan MakielskiSummaryAffiliation: University of Wisconsin Country: USA Publications
Research Grants
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Detail Information
Publications
Intrinsic lidocaine affinity for Na channels expressed in Xenopus oocytes depends on alpha (hH1 vs. rSkM1) and beta 1 subunitsJ C Makielski
Department of Medicine, University of Wisconsin, Madison 53792, USA
Cardiovasc Res 42:503-9. 1999..Inactivation kinetics, however, depend upon the alpha-subunit isoform and the presence of the auxiliary beta 1-subunit and will affect measures of block...
SIDS: genetic and environmental influences may cause arrhythmia in this silent killerJonathan C Makielski
Department of Medicine, Cardiovascular Medicine Section and Department of Physiology, University of Wisconsin, Madison, Wisconsin 53792, USA
J Clin Invest 116:297-9. 2006....- A ubiquitous splice variant and a common polymorphism affect heterologous expression of recombinant human SCN5A heart sodium channelsJonathan C Makielski
Department of Medicine, University of Wisconsin, 600 Highland Ave H6 349, Madison, Wis 53792, USA
Circ Res 93:821-8. 2003..These results have implications for the choice of background sequence for experiments with heterologous expression systems, and possibly implications for electrophysiological function in vivo... - Ranolazine and late cardiac sodium current--a therapeutic target for angina, arrhythmia and more?Jonathan C Makielski
Department of Medicine, Cardiovascular Medicine Section, University of Wisconsin, Madison, WI 53705, USA
Br J Pharmacol 148:4-6. 2006..This commentary discusses the implications of that study and the background and implications for block of late cardiac sodium current in general... - Partial expression defect for the SCN5A missense mutation G1406R depends on splice variant background Q1077 and rescue by mexiletineBi Hua Tan
Dept of Medicine, Univ of Wisconsin, 600 Highland Ave H6 349, Madison, WI 53792, USA
Am J Physiol Heart Circ Physiol 291:H1822-8. 2006..These data show that a trafficking defect may be partial and time dependent and may differ with the splice variant background. Also, expression defects and gating abnormalities may contribute to loss of function for the same mutation... - Na(+) current in human ventricle: implications for sodium loading and homeostasisJonathan C Makielski
Department of Medicine, Cardiovascular Medicine Section, University of Wisconsin, Madison, Wisconsin 53792, USA
J Cardiovasc Electrophysiol 17:S15-S20. 2006.... - Alpha1-syntrophin mutations identified in sudden infant death syndrome cause an increase in late cardiac sodium currentJianding Cheng
Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin, Madison, WI, USA
Circ Arrhythm Electrophysiol 2:667-76. 2009..This study determined the prevalence and functional properties of SIDS-associated SNTA1 mutations... - A trafficking defective, Brugada syndrome-causing SCN5A mutation rescued by drugsCarmen R Valdivia
Department of Medicine and Physiology, University of Wisconsin, Madison, WI, USA
Cardiovasc Res 62:53-62. 2004..Whether the mutant channel may be rescued in vivo by mexiletine and normalize the patient's electrophysiologic parameters remains to be tested... - Epidemiologic, molecular, and functional evidence suggest A572D-SCN5A should not be considered an independent LQT3-susceptibility mutationDavid J Tester
Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
Heart Rhythm 7:912-9. 2010..Considering that approximately 2% of Caucasian controls host rare, nonsynonymous variants in the SCN5A-encoded cardiac sodium channel, caution must be exercised when interpreting SCN5A genetic test results for long QT syndrome (LQTS)... - Syntrophin mutation associated with long QT syndrome through activation of the nNOS-SCN5A macromolecular complexKazuo Ueda
Department of Medicine, University of Wisconsin, Madison, WI 53792, USA
Proc Natl Acad Sci U S A 105:9355-60. 2008..These results establish an SNTA1-based nNOS complex attached to SCN5A as a key regulator of sodium current and suggest that SNTA1 be considered a rare LQTS-susceptibility gene... - KCNJ2 mutations in arrhythmia patients referred for LQT testing: a mutation T305A with novel effect on rectification propertiesLee L Eckhardt
Department of Medicine Cardiovascular Medicine, University of Wisconsin, Madison, WI 53792, USA
Heart Rhythm 4:323-9. 2007..Do KCNJ2 mutations occur in patients lacking this triad and lacking a family history of ATS?.. - GPD1L links redox state to cardiac excitability by PKC-dependent phosphorylation of the sodium channel SCN5ACarmen R Valdivia
Department of Medicine, University of Wisconsin Madison, Madison, Wisconsin, USA
Am J Physiol Heart Circ Physiol 297:H1446-52. 2009.... - A common human SCN5A polymorphism modifies expression of an arrhythmia causing mutationBin Ye
Department of Medicine and Physiology, University of Wisconsin, Madison, Wisconsin 53792, USA
Physiol Genomics 12:187-93. 2003..These results show that the choice of background clone must be carefully considered in mutagenesis studies. This also represents an example of intragenic complementation, the first for such a large protein... - Rate-dependent QT shortening mechanism for the LQT3 deltaKPQ mutantToshihisa Nagatomo
Department of Medicine, Cardiology Section, University of Wisconsin, Madison, WI 53792, USA
Cardiovasc Res 54:624-9. 2002..This provides a mechanism correlating the genotype with the clinical phenotype, and provides a rationale for the effectiveness of pacemaker therapy in LQT3 patients... - Common human SCN5A polymorphisms have altered electrophysiology when expressed in Q1077 splice variantsBi-Hua Tan
Department of Medicine, Cardiovascular Section, University of Wisconsin, Madison, Wisconsin 53792, USA
Heart Rhythm 2:741-7. 2005..These findings have implications for the interpretation of previous studies of arrhythmia mutations. The significance of these findings for clinical arrhythmia remains to be elucidated... - Loss-of-function mutation of the SCN3B-encoded sodium channel {beta}3 subunit associated with a case of idiopathic ventricular fibrillationCarmen R Valdivia
Department of Medicine, Cardiovascular Section, and the Cardiac Molecular Arrhythmias Research Program, University of Wisconsin Madison, 600 Highland Avenue H6 349, Madison, WI 53792, USA
Cardiovasc Res 86:392-400. 2010..5 is regulated by four sodium channel auxiliary beta subunits. Here, we report a case with IVF and a novel mutation in the SCN3B-encoded sodium channel beta subunit Navbeta3 that causes a loss of function of Nav1.5 channels in vitro... - A novel C-terminal truncation SCN5A mutation from a patient with sick sinus syndrome, conduction disorder and ventricular tachycardiaBi Hua Tan
Department of Medicine, Cardiovascular Section, University of Wisconsin Madison, 600 Highland Ave H6 349, Madison, WI 53792, USA
Cardiovasc Res 76:409-17. 2007..Here we report a family harboring an SCN5A mutation (L1821fs/10) causing a truncation of the C-terminus with a marked and complex biophysical phenotype and a corresponding variable and complex clinical phenotype with variable penetrance... - A novel SCN5A arrhythmia mutation, M1766L, with expression defect rescued by mexiletineCarmen R Valdivia
Departments of Medicine and Physiology, University of Wisconsin, Madison, WI, USA
Cardiovasc Res 55:279-89. 2002.... - Protein kinase A-dependent biophysical phenotype for V227F-KCNJ2 mutation in catecholaminergic polymorphic ventricular tachycardiaAmanda L Vega
Department of Medicine, University of Wisconsin, Madison, Wisconsin 53792, USA
Circ Arrhythm Electrophysiol 2:540-7. 2009..The aim of this study was to characterize the biophysical and cellular phenotype of a KCNJ2 missense mutation, V227F, found in a patient with catecholaminergic polymorphic ventricular tachycardia... - Unique mixed phenotype and unexpected functional effect revealed by novel compound heterozygosity mutations involving SCN5AArgelia Medeiros-Domingo
Department of Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota 55905, USA
Heart Rhythm 6:1170-5. 2009.... - Molecular identification and functional characterization of a mitochondrial sulfonylurea receptor 2 splice variant generated by intraexonic splicingBin Ye
Department of Medicine, University of Wisconsin, Madison, WI 53706, USA
Circ Res 105:1083-93. 2009..Cardioprotective pathways may involve a mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel but its composition is not fully understood... - Increased late sodium current in myocytes from a canine heart failure model and from failing human heartCarmen R Valdivia
Departments of Medicine, Surgery and Physiology, University of Wisconsin Hospital and Clinics, University of Wisconsin, 600 Highland Avenue H6/349, Madison, WI 53792, USA
J Mol Cell Cardiol 38:475-83. 2005..We conclude that a peak I(Na) is decreased, and non-inactivating late I(Na) is increased in heart failure and this may contribute to action potential prolongation and the generation of arrhythmia... - Late Na currents affected by alpha subunit isoform and beta1 subunit co-expression in HEK293 cellsCarmen R Valdivia
Departments of Medicine and Physiology, University of Wisconsin, 600 Highland Avenue, Madison, WI 53792, USA
J Mol Cell Cardiol 34:1029-39. 2002..These properties may provide mechanisms for regional and transmural distribution of late Na current and late Na current amplitudes during development and in disease states... - Specific serine proteases selectively damage KCNH2 (hERG1) potassium channels and I(Kr)Sridharan Rajamani
Department of Medicine Cardiology, University of Wisconsin, Madison 53792, USA
Am J Physiol Heart Circ Physiol 290:H1278-88. 2006.... - Function and distribution of the SUR isoforms and splice variantsNian-Qing Shi
Department of Medicine, Cardiovascular Medicine Section, University of Wisconsin, Madison, WI 53705, USA
J Mol Cell Cardiol 39:51-60. 2005..x subunits. The different isoforms and splice variants allow for many K(ATP) channel combinations, and therefore, increases the channel diversity and the possibility of complexity in function... - Cardiac sulfonylurea receptor short form-based channels confer a glibenclamide-insensitive KATP activityJie lin Pu
Department of Medicine, University of Wisconsin, 1300, University Ave, Room 24, SMI Building, Madison, WI 53706, USA
J Mol Cell Cardiol 44:188-200. 2008..1 or Kir6.2 suggesting that the short forms may function as hemi-transporters reported in other eukaryotic ABC transporter subgroups. Our results indicate that different K(ATP) compositions may co-exist in cardiac sarcolemmal membrane... - The mitochondrial bioenergetic phenotype for protection from cardiac ischemia in SUR2 mutant miceNitin T Aggarwal
Department of Medicine, University of Wisconsin, Madison, USA
Am J Physiol Heart Circ Physiol 299:H1884-90. 2010..These results have implications for possible SUR2 participation in mitochondrial K(ATP)... - Genetic basis for the origin of cardiac arrhythmias: implications for therapyMackenzi Mbai
University of Wisconsin Hospitals and Clinics, Section of Cardiovascular Medicine, Room H6/354 CSC (3248, 600 Highland Avenue, Madison, WI 53792, USA
Curr Cardiol Rep 4:411-7. 2002..New therapies based on this evolving insight are being developed. This review summarizes recent discoveries with a focus on the genetic basis of cardiac arrhythmias and their implications for new therapies... - Intrinsic mechanism of the enhanced rate-dependent QT shortening in the R1623Q mutant of the LQT3 syndromeYasushi Oginosawa
Second Department of Internal Medicine, University of Occupational and Environmental Health Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan
Cardiovasc Res 65:138-47. 2005..Our findings are important for genotype-phenotype correlations in LQT3 mutants as well as for understanding the function of S4 segment of domain IV region in the cardiac Na(+) channel... - Blockade of HERG cardiac K+ current by antifungal drug miconazoleKan Kikuchi
Second Department of Internal Medicine, University of Occupational and Environmental Health Japan, Kitakyushu, Japan
Br J Pharmacol 144:840-8. 2005..Thus, miconazole prolongs the QT interval by direct inhibition of HERG channels... - SCN4B-encoded sodium channel beta4 subunit in congenital long-QT syndromeArgelia Medeiros-Domingo
Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico
Circulation 116:134-42. 2007..Four different beta-subunits have been described. All are detectable in cardiac tissue, but none have yet been linked to any heritable arrhythmia syndrome... - Spectrum and prevalence of cardiac sodium channel variants among black, white, Asian, and Hispanic individuals: implications for arrhythmogenic susceptibility and Brugada/long QT syndrome genetic testingMichael J Ackerman
Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
Heart Rhythm 1:600-7. 2004..The purpose of this study was to determine the prevalence and spectrum of nonsynonymous polymorphisms (amino acid variants) in the cardiac sodium channel among healthy subjects... - The perplexing complexity of cardiac arrhythmias: beyond electrical remodelingPhilip B Adamson
University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
Heart Rhythm 2:650-9. 2005..Approaches are recommended for future investigations focused on providing new mechanistic insights and therapeutic interventions... - Suppression of atrial fibrillation with mexiletine pharmacotherapy in a young woman with type 1 long QT syndromeMalek El Yaman
Department of Pediatrics/Division of Pediatric Cardiology, Mayo Clinic, Rochester, MN 55905, USA
Heart Rhythm 5:472-4. 2008 - A mutation in telethonin alters Nav1.5 functionAmelia Mazzone
Enteric Neuroscience Program, Mayo Clinic, Rochester, Minnesota 55905, USA
J Biol Chem 283:16537-44. 2008..These results suggest a new role for telethonin, namely that telethonin is a sodium channel-interacting protein. Also, mutations in telethonin can alter Na(v)1.5 kinetics and may play a role in intestinal pseudo-obstruction... - The single nucleotide polymorphisms of I(Ks) potassium channel genes and their association with atrial fibrillation in a Chinese populationZhiyu Zeng
Center for Arrhythmia Diagnosis and Treatment, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Cardiology 108:97-103. 2007..1% respectively, OR = 1.66, p = 0.044). We provided the frequencies of non-synonymous SNPs of KCNQ1 and KCNE1 in Chinese population; none of these SNPs was associated with AF. But KCNE4 E145D may be associated with the AF phenotype... - Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndromeMatteo Vatta
Department of Pediatrics Cardiology, Baylor College of Medicine, Texas Children s Hospital, Houston, TX 77030, USA
Circulation 114:2104-12. 2006.... - Molecular and functional characterization of novel glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) mutations in sudden infant death syndromeDavid W Van Norstrand
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA
Circulation 116:2253-9. 2007..We hypothesized that mutations in GPD1-L may be responsible for some cases of sudden unexplained death/sudden infant death syndrome... - Novel mechanism for sudden infant death syndrome: persistent late sodium current secondary to mutations in caveolin-3Lisa B Cronk
Mayo Medical School, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
Heart Rhythm 4:161-6. 2007..We recently established CAV3-encoded caveolin-3 as a novel LQTS-associated gene with mutations producing a gain-of-function, LQT3-like molecular/cellular phenotype... - Inherited arrhythmias: a National Heart, Lung, and Blood Institute and Office of Rare Diseases workshop consensus report about the diagnosis, phenotyping, molecular mechanisms, and therapeutic approaches for primary cardiomyopathies of gene mutations affeStephan E Lehnart
Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, College of Physicians and Surgeons of Columbia University, P and S 9 401 box 22, 630 W 168 St, New York, NY 10032, USA
Circulation 116:2325-45. 2007.... - Arrhythmia mutations in non-coding region of SCN5A: implications for genetic screeningJonathan C Makielski
J Mol Cell Cardiol 38:551-3. 2005 - Mice lacking sulfonylurea receptor 2 (SUR2) ATP-sensitive potassium channels are resistant to acute cardiovascular stressDouglas Stoller
Committee on Cell Physiology, The University of Chicago, Chicago, IL 60637, USA
J Mol Cell Cardiol 43:445-54. 2007..We conclude that conventional sarcolemmal cardiomyocyte K(ATP) channels containing full-length SUR2 are not required for mediating the response to acute cardiovascular stress... - Genotypic heterogeneity and phenotypic mimicry among unrelated patients referred for catecholaminergic polymorphic ventricular tachycardia genetic testingDavid J Tester
Department of Molecular Pharmacology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
Heart Rhythm 3:800-5. 2006..Mutations in the RyR2-encoded cardiac ryanodine receptor/calcium release channel and in CASQ2-encoded calsequestrin cause catecholaminergic polymorphic ventricular tachycardia (CPVT1 and CPVT2, respectively)...
Research Grants
- Molecular Regulation - Cardiac KATP Channels in IschemiaJonathan Makielski; Fiscal Year: 2006..It will also provide important new information on mitochondrial structure and function in heart. ..
- Cellular & Clinical Phenotypes of Novel SCN5a MutationsJonathan Makielski; Fiscal Year: 2006..At a more basic level these "natural" experiments will contribute to understanding the structure-function relationship of this important channel. ..
- TRAINING PROGRAM IN TRANSLATIONAL CARDIOVASCULAR SCIENCEJonathan Makielski; Fiscal Year: 2007..End of Abstract) ..
- Molecular Regulation of Cardiac KATP Channels in IschemiaJonathan Makielski; Fiscal Year: 2009..The results may suggest more specific therapeutic targets in the SUR2 variants, and it will also provide important new information on mitochondrial structure and function in heart. ..
- Molecular Regulation of Cardiac KATP Channels in IschemiaJonathan C Makielski; Fiscal Year: 2010..The results may suggest more specific therapeutic targets in the SUR2 variants, and it will also provide important new information on mitochondrial structure and function in heart. ..
- MOLECULAR REGULATION--CARDIAC K+ATP CHANNELS IN ISCHEMIAJonathan Makielski; Fiscal Year: 2001....
- REGULATION OF LATE INWARD CURRENT IN HUMAN HEART FAILUREJonathan Makielski; Fiscal Year: 2003....
- Cellular and clinical phenotypes of novel SCN5a mutationsJonathan C Makielski; Fiscal Year: 2010..The results are expected to improve diagnosis of these inherited syndromes and suggest ways to treat and prevent them. ..