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Thomas Jefferson University - Manuel L. Covarrubias, MD, PhD
Manuel L. Covarrubias, MD, PhD

Thomas Jefferson University,Jefferson Medical College,Department of Neuroscience
Appointed: 2004
Mailing Address
900 Walnut Street
Philadelphia, Pennsylvania 19107
United States
Contact Information
Phone: (215) 503-4341
M.D., National University of Mexico, 1978

Ph.D., National University of Mexico, Chemistry, 1980

Postdoctoral Training:

Max-Planck-Institut fuer Ernaehrungsphysiologie, Dortmund, Germany

Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO

Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO
Expertise and Research Interests

Voltage-gated potassium channels; molecular mechanisms underlying function, regulation and interactions with drugs.


The research in my laboratory focuses on voltage-gated potassium channels expressed in brain and heart. We investigate the molecular mechanisms governing the function and regulation of these ion channels. These studies can impact our understanding of neuronal plasticity, epilepsy, chronic pain, arrhythmias, anesthesia and alcohol intoxication. Furthermore, they may unveil potential drug-targets. The research platform of our work is based on a modern multidisciplinary approach, which applies electrophysiology, molecular biology, biochemistry, pharmacology and mathematical modeling.

Other Expertise

Physiological Sciences Study Section (NIH). 1995-1996.

MBPP (Membrane Biology & Protein Processing) Study Section (NIH). Regular member from 2005 - 2008.

National Science Foundation. Ad hoc reviewer, 1995, 2008.

Medical Research Council, UK. Ad hoc reviewer, 2007.

Manuscript Reviewer (since 1991): J. Biol. Chem.; J. Gen. Physiol.; Biophys. J.; J. Physiol. (London); Am. J. Physiol. (Cell Physiol.); FEBS Lett.; Proc. Nat. Acad. Sci. USA; J. Neurosci.; Mol. Cell Neurosci; Nature Chem. Biol.


Faculty member of the Ph.D. programs in Cell and Developmental Biology, Molecular Physiology and Biophysics, and Neuroscience at Thomas Jefferson University.

Molecular Approaches to Ion Channel Structure and Function: a Laboratory Course. (sponsored by the Howard Hughes Medical Institute). April 20-May 2, 1997. CINVESTAV, Mexico City.

Graduate Courses: Advanced Cell Biology (CB611); Introduction to Neuroscience (NS700); Molecular and Cellular Neuroscience (NS715); Applications of Statistics in Neuroscience (NS740); Molecular Pharmacology (PR680); Foundations in Biomedical Sciences (GC550); Neurosurgery Board Review: Neuroanatomy and Neurophysiology.

Medical School Courses: Neuroscience (MCBM, ID150).

Course director of CB611 (Advanced Topics in Molecular Cell Biology). 2004-2010

Course co-director (Cell Signaling). 2011-

Chair of the Curriculum Committee, The Neuroscience Ph.D. Program, Thomas Jefferson University.


Tapan B. Vyas (1992-1995); Laura Escobar (1994-1995); Henry H. Jerng (1993-1998); Mohammad Shahidullah (1997-2003); Edward J. Beck (1997-2001); Maria T. Pacheco-Cano (1998-1999); Ricardo Hernandez-Pineda (1999-2000); Carmen A. Rocha (2001-2003); Benjamin Kaplan (2002-2004); Thanawath Harris (2002-2008 ); Guangyu Wang (2003-2007); Kevin Dougherty (2004-2008); Jose A. De Santiago-Castillo (2006-2008); Jeffrey Fineberg (2009- ); Annika Fitzpatrick (2009- ); David Ritter (2009- ).
potassium channel; voltage-gated potassium channel; K channel; Kv4 potassium channel; KChIP; DPP6; somatodendritic potassium channels; alkanol; anesthetic; channel inactivation; neuronal channel; cardiac channel; electrophysiology; patch-clamp
  • SELECTED (2004- )
  • Jerng, H.H., Pfaffinger, P.J. and Covarrubias, M. (2004). Molecular Physiology and Modulation of the Somatodendritic A-type Potassium Channel. Molecular and Cellular Neuroscience 27: 343-369.
  • Covarrubias, M., Bhattacharji, A., Kaplan, B., Harris, T. and Germann, M.W. (2005). Alcohol and anesthetic action at the gate of a voltage-gated K+ channel. In Basic and Systemic Mechanisms of Anesthesia (Mashimo, T., Ogli, K. & Uchida I. ed.). International Congress Series 1283, Elsevier, The Netherlands, pp. 55-60.
  • Wang, G., Shahidullah, M., Rocha, C.A., Strang, C., Pfaffinger, P.J. and Covarrubias, M. (2005). Functionally active T1-T1 interfaces revealed by the accessibility of intracellular thiolate groups in Kv4 channels. J. Gen. Physiol. 126:55-69.
  • Wang, G. and Covarrubias, M. (2006). Voltage-dependent gating rearrangements in the intracellular T1-T1 interface of a Kv channel. J. Gen. Physiol. 127:391-400.
  • Bhattacharji, A. Kaplan, B., Harris, T., Qu, X., Germann, M. W. and Covarrubias, M. (2006). The concerted contribution of the S4-S5 linker and the S6 segment to the modulation of a Kv channel by 1-alkanols. Mol. Pharm. 70:1542-54.
  • Fawcett, G.L., Santi, C., Butler, A., Harris, T., Covarrubias, M. and Salkoff, L. (2006). Mutant Analysis of the Shal (Kv4) voltage-gated fast transient K+ channel in C. elegans. J. Biol. Chem. 281:30725-35.
  • Dougherty, K. and Covarrubias, M. (2006). A dipeptidyl aminopeptidase protein remodels gating charge dynamics in Kv4.2 channels. J. Gen. Physiol. 128:745-53.
  • Wang, G., Strang, C., Pfaffinger, P.J. and Covarrubias, M. (2007). Zn++dependent redox switch in the intracellular T1-T1 interface of a Kv4 channel. J. Biol. Chem. 282:13637-13647.
  • Rojas, P., Garst-Orozco, J., Baban, B., De Santiago-Castillo, J.A., Covarrubias, M. and Salkoff, L. (2008). Cumulative activation of a voltage-dependent potassium channel. J. Neurosci. 28:757-765.
  • Kaulin, Y.A., De Santiago-Castillo, J.A., Rocha, C.A. and Covarrubias, M. (2008). Mechanism of the modulation of Kv4.3:KChIP1 channels by elevated external K+. Biophys. J. 94:1241-1251.
  • Dougherty, K., De Santiago-Castillo, J.A. & Covarrubias, M. (2008). Gating charge immobilization in Kv4.2 channels: the basis of closed-state inactivation. J. Gen. Physiol. 131:257-73.
  • Amarillo, Y. De Santiago-Castillo, J.A., Dougherty, K., Kwon, E., Covarrubias, M. and Rudy, B. (2008). Ternary Kv4.2 channels recapitulate voltage-dependent inactivation kinetics of A-type K+ channels in cerebellar granule neurons. J. Physiol. (London) 586.8:2093-2106.
  • Covarrubias, M., Bhattacharji, A., De Santiago-Castillo, J.A., Dougherty, K., Kaulin, Yu. A., Ratanadilok Na Phuket, T. and Wang, G. (2008). The Neuronal Kv4 Channel Complex (peer-reviewed mini-review article by invitation). Neurochem. Res. 33:1558-1567.
  • Schwenk, J., Zolles, G., Kandias, N.G., Neubauer, I., Kalbacher, H., Covarrubias, M., Fakler, B. and Bentrop, D. (2008). NMR analysis of KChIP4a reveals structural basis for the control of surface expression of Kv4 channel complexes. J. Biol. Chem. 283:18937-18946.
  • Kaulin, Y., De Santiago-Castillo, J.A., Nadal., M., Rudy, B. and Covarrubias, M. (2009). The dipeptidyl-peptidase-like-protein DPP6 determines the unitary conductance of neuronal Kv4.2 channels. J. Neurosci. 29:3242-3251.
  • Dougherty, K., Tu, L., Deutsch, C. and Covarrubias, M. (2009). The dipeptidyl-aminopeptidase-like protein-6 is an integral voltage sensor interacting b-subunit of neuronal Kv4.2 channels. Channels 3(2):122-128.
  • Ratadanilok Na Phuket, T. and Covarrubias, M. (2009). Kv4 channels underlie the subthreshold-operating A-type K+ current in dorsal root ganglion neurons. Frontiers in Molecular Neuroscience 2:1-14.
  • Jerng H.H., Dougherty K., Covarrubias M., Pfaffinger P.J. (2009). A novel N-terminal motif of dipeptidyl peptidase-like proteins produces rapid inactivation of Kv4.2 channels by a pore-blocking mechanism. Channels (Austin) 3(6):1-14.
  • Eckenhoff, R., Xi, J., Shimaoka, M., Bhattacharji, A., Covarrubias, M., Dailey, W. (2010). Azi-isoflurane, a photolabel analog of the commonly used inhaled general anesthetic, isoflurane. ACS Chemical Neuroscience 1(2):139-145.
  • Bhattacharji, A., Klett, N., Go, R.C.V. and Covarrubias, M. (2010). Inhalational anesthetics and n-alcohols share a site of action in the neuronal Shaw2 Kv channel. British J. Pharm. 159(7):1475-85.
  • De Santiago-Castillo, J.A., Covarrubias, M., Sánchez-Rodríguez, J.E., Perez-Cornejo, P., Arreola, J. (2010). Simulating complex ion channel kinetics with IonChannelLab. Channels 4:422-8.
  • Bähring, R. and Covarrubias, M. (2011). Mechanisms of closed state inactivation in voltage-gated ion channels (peer-reviewed Topical Review by invitation) J. Physiol. 589(Pt 3):461-79.

Individual Expertise profile of Manuel L. Covarrubias, MD, PhD, Copyright © Manuel L. Covarrubias, MD, PhD.
Last Updated by Manuel Covarrubias, MD, PhD : Wednesday, April 6, 2011 11:51:45 AM

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