Jonathan C. Makielski MD

Professor
Departments of Medicine (Cardiology) and Physiology
jcm@medicine.wisc.edu

Senior Associate Chair for Research, Department of Medicine

Trainer in the Following Programs:

  • Director Research Training, Cardiovascular Research Center
  • Molecular and Cellular Pharmacology Program
  • Department of Physiology

Awards and Honors:

  • Pfizer Fellowship
  • NIH Physician Scientist Award
  • Syntex Scholars Finalist

Dr. Makielski, examines the role of ion channels in cardiovascular disease, particularly the voltage-gated sodium channel and inward rectifier potassium channels such as the ATP-sensitive potassium channel (KATP). His lab uses voltage-clamp techniques to investigate the biophysics, pharmacology, and regulation of these channels in control and diseased native myocytes, and recombinant DNA techniques to investigate cloned wild type and mutated channels expressed in heterologous systems such as HEK cells. Particular interests are: 1) antiarrhythmic drug binding to the sodium channel, 2) long QT mutations in the sodium channel, 3) regulatory sites on SUR and Kir6.x, the subunits of KATP, 4) regulation of KATP activity under conditions found in ischemia such as acidosis and altered phospholipid metabolism, 5) alterations in ion channel function in disease states such as heart failure, and the role of ion channels in arrhythmia. These investigations are motivated by importance of these channels for arrhythmogenesis and the pathophysiology of myocardial ischemia.

Selected Bibliography:

  • Makielski JC, Farley AL. (2006) Na(+) current in human ventricle: implications for sodium loading and homeostasis. J Cardiovasc Electrophysiol. 17 Suppl 1:S15-S20.

  • Tan BH, Valdivia CR, Song C, Makielski JC. (2006) Partial expression defect for the SCN5A missense mutation G1406R depends on splice variant background Q1077 and rescue by mexiletine. Am J Physiol Heart Circ Physiol. 291(4):H1822-8.

  • Makielski JC, Valdivia CR. (2006) Ranolazine and late cardiac sodium current--a therapeutic target for angina, arrhythmia and more? Br J Pharmacol. 148(1):4-6.

  • Makielski JC.(2006) SIDS: genetic and environmental influences may cause arrhythmia in this silent killer. J Clin Invest. 116(2):297-9.

  • Rajamani S, Anderson CL, Valdivia CR, Eckhardt LL, Foell JD, Robertson GA, Kamp TJ, Makielski JC, Anson BD, January CT. (2006) Specific serine proteases selectively damage KCNH2 (hERG1) potassium channels and I(Kr). Am J Physiol Heart Circ Physiol. 290(3):H1278-88.

  • Tan BH, Valdivia CR, Rok BA, Ye B, Ruwaldt KM, Tester DJ, Ackerman MJ, and Makielski JC. (2005). Common human SCN5A polymorphisms have altered electrophysiology when expressed in Q1077 splice variants. Heart Rhythm. 2:741-747.

  • Shi NQ, Ye B, and Makielski JC. (2005). Function and distribution of the SUR isoforms and splice variants. J Mol Cell Cardiol. 39:51-60.

  • Valdivia CR, Tester DJ, Rok BA, Porter CB, Munger TM, Jahangir A, Makielski JC and Ackerman MJ. (2004) A trafficking defective, Brugada syndrome-causing SCN5A mutation rescued by drugs. Cardiovasc Res 62:53-62 2004

  • J.C. Makielski , B. Ye, C.R. Valdivia, M.D. Pagel, J. Pu, D.J. Tester, M.J. Ackerman. (2003) A Ubiquitous Splice Variant and a Common Polymorphism Affect Heterologous Expression of Recombinant Human SCN5A Heart Sodium Channels. Circ Res.93:821-828.

  • B. Ye, C. R. Valdivia, M. J. Ackerman, J. C Makielski. (2003) A common human SCN5A polymorphism modifies expression of an arrhythmia causing mutation. Physiological Genomics 12(3):187-193.

  • W.A. Chutkow, J. Pu, M.T. Wheeler, T. Wada, J.C. Makielski, C.F. Burant, E.M. McNally (2002) Printzmetal like vasospasm, hypertension, and early death result from the absence of SUR2 KATP channels in mice. J. Clin. Invest 110:203-208.

  • C.R. Valdivia, M.J. Ackerman, D.A. Tester, T. Wada, J. McCormack, B. Ye, J.C. Makielski. (2002) A novel SCN5A arrhythmia mutation M1766L with expression defect rescued by mexiletine. Cardiovasc Res. 54(3):624-629.

  • Valdivia, C.R., Nagatomo, T., and Makielski, J.C. (2002) Late currents affect kinetics for heart and skeletal Na channel a and b1 subunits expressed in HEK293 cells. J. Mol. and Cellular Cardiology 34:1029-1039.

  • Nagatomo, T., January, C.T., Ye, B., Abe, H., Nakashima, Y., and Makielski, J.C. (2002) Rate-dependent QT shortening mechanism for the LQT3 deltaKPQ mutant. Cardiovascular Res. 54:624-629.

  • Chutkow, W.A., Samuel1, V., Hansen, P.A., Pu, J., Valdivia, C.R., Makielski, J.C. and Burant, C.F. (2001) Disruption of Sur2 containing KATP channels enhances insulin stimulated glucose uptake in skeletal muscle. PNAS 98:11760-11764.

  • Ackerman, M.J., Siu, B.L., Sturner, W.Q., Tester, D.A., Valdivia, C.R., Makielski, J.C. and Towbin, J. (2001) Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome. JAMA 286:2264-2269.

  • Nagatomo, T., January, C.T., and Makielski J.C. (2000) Preferential block of late INa in the LQT3 deltaKPQ mutant by the class IC antiarrhythmic flecainide. Molecular Pharm. 57: 101-107.

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