Manuel Covarrubias

TitleProfessor
InstitutionThomas Jefferson University
DepartmentDepartment of Neurosciences
Address900 Walnut Street
Philadelphia PA 19107
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    PEER REVIEW EXPERTISE (1991- )

    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.

    TEACHING EXPERTISE (1992- )

    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.

    FORMER AND CURRENT GRADUATE STUDENTS AND POSTDOCTORAL FELLOWS

    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- ).


    Collapse Research 
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    R29NS032337     (COVARRUBIAS, MANUEL L)Dec 15, 1993 - May 23, 1999
    NIH
    MOLECULAR REGULATION OF POTASSIUM CHANNELS
    Role: Principal Investigator

    R01NS032337     (COVARRUBIAS, MANUEL L)Dec 15, 1993 - May 31, 2012
    NIH
    Gating of Neuronal Kv4 Channels
    Role: Principal Investigator

    R01AA010615     (COVARRUBIAS, MANUEL L)Jan 1, 1997 - Jan 31, 2013
    NIH
    Mapping the alcohol site of a neuronal potassium channel
    Role: Principal Investigator

    R21NS079855     (COVARRUBIAS, MANUEL L)Jul 1, 2013 - Dec 31, 2015
    NIH
    Neuromodulation of Kv3.4 channels in nociceptors
    Role: Principal Investigator

    R01NS110385     (LEPORE, ANGELO C.)Sep 1, 2018 - Aug 31, 2023
    NIH
    Exploring the EphB2-NMDA receptor interaction in spinal cord injury-induced neuropathic pain
    Role: Co-Principal Investigator

    Collapse Bibliographic 
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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Ojala KS, Ginebaugh SP, Wu M, Miller EW, Ortiz G, Covarrubias M, Meriney SD. A high affinity, partial antagonist effect of 3,4-diaminopyridine mediates action potential broadening and enhancement of transmitter release at NMJs. J Biol Chem. 2021 Jan 16; 100302. PMID: 33465376.
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    2. Zemel BM, Zhi L, Brown EV, Tymanskyj SR, Liang Q, Covarrubias M. PKCe associates with the Kv3.4 channel to promote its expression in a kinase activity-dependent manner. FASEB J. 2021 Jan; 35(1):e21241. PMID: 33368632.
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    3. Zemel BM, Ritter DM, Covarrubias M, Muqeem T. A-Type KV Channels in Dorsal Root Ganglion Neurons: Diversity, Function, and Dysfunction. Front Mol Neurosci. 2018; 11:253. PMID: 30127716.
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    4. Yang E, Granata D, Eckenhoff RG, Carnevale V, Covarrubias M. Propofol inhibits prokaryotic voltage-gated Na+ channels by promoting activation-coupled inactivation. J Gen Physiol. 2018 Sep 03; 150(9):1299-1316. PMID: 30018038.
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    5. Wang Y, Yang E, Wells MM, Bondarenko V, Woll K, Carnevale V, Granata D, Klein ML, Eckenhoff RG, Dailey WP, Covarrubias M, Tang P, Xu Y. Propofol inhibits the voltage-gated sodium channel NaChBac at multiple sites. J Gen Physiol. 2018 Sep 03; 150(9):1317-1331. PMID: 30018039.
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    6. Cheng L, Al-Owais MM, Covarrubias M, Koch WJ, Manning DR, Peers C, Riobo-Del Galdo N. Coupling of Smoothened to inhibitory G proteins reduces voltage-gated K+ currents in cardiomyocytes and prolongs the cardiac action potential duration. J Biol Chem. 2018 May 25. PMID: 29802197.
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    7. Yang E, Zhi L, Liang Q, Covarrubias M. Electrophysiological Analysis of Voltage-Gated Ion Channel Modulation by General Anesthetics. Methods Enzymol. 2018; 602:339-368. PMID: 29588038.
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    8. Muqeem T, Ghosh B, Pinto V, Lepore AC, Covarrubias M. Regulation of nociceptive glutamatergic signaling by presynaptic Kv3.4 channels in the rat spinal dorsal horn. J Neurosci. 2018 Mar 14. PMID: 29540546.
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    9. Woll KA, Zhou X, Bhanu NV, Garcia BA, Covarrubias M, Miller KW, Eckenhoff RG. Identification of binding sites contributing to volatile anesthetic effects on GABA type A receptors. FASEB J. 2018 Aug; 32(8):4172-4189. PMID: 29505303.
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    10. Zemel BM, Muqeem T, Brown EV, Goulão M, Urban MW, Tymanskyj SR, Lepore AC, Covarrubias M. Calcineurin dysregulation underlies spinal cord injury-induced K+ channel dysfunction in DRG neurons. J Neurosci. 2017 Jul 27. PMID: 28751455.
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    11. Woll KA, Peng W, Liang Q, Zhi L, Jacobs JA, Maciunas L, Bhanu N, Garcia BA, Covarrubias M, Loll PJ, Dailey WP, Eckenhoff RG. Photoaffinity Ligand for the Inhalational Anesthetic Sevoflurane Allows Mechanistic Insight into Potassium Channel Modulation. ACS Chem Biol. 2017 05 19; 12(5):1353-1362. PMID: 28333442.
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    12. Bu W, Liang Q, Zhi L, Maciunas L, Loll PJ, Eckenhoff RG, Covarrubias M. Sites and Functional Consequence of Alkylphenol Anesthetic Binding to Kv1.2 Channels. Mol Neurobiol. 2018 02; 55(2):1692-1702. PMID: 28204960.
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    13. Fineberg JD, Szanto TG, Panyi G, Covarrubias M. Closed-state inactivation involving an internal gate in Kv4.1 channels modulates pore blockade by intracellular quaternary ammonium ions. Sci Rep. 2016; 6:31131. PMID: 27502553.
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    14. Woll KA, Murlidaran S, Pinch BJ, Hénin J, Wang X, Salari R, Covarrubias M, Dailey WP, Brannigan G, Garcia BA, Eckenhoff RG. A Novel Bifunctional Alkylphenol Anesthetic Allows Characterization of ?-Aminobutyric Acid, Type A (GABAA), Receptor Subunit Binding Selectivity in Synaptosomes. J Biol Chem. 2016 09 23; 291(39):20473-86. PMID: 27462076.
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    15. Liang Q, Anderson WD, Jones ST, Souza CS, Hosoume JM, Treptow W, Covarrubias M. Positive Allosteric Modulation of Kv Channels by Sevoflurane: Insights into the Structural Basis of Inhaled Anesthetic Action. PLoS One. 2015; 10(11):e0143363. PMID: 26599217.
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    16. Covarrubias M, Barber AF, Carnevale V, Treptow W, Eckenhoff RG. Mechanistic Insights into the Modulation of Voltage-Gated Ion Channels by Inhalational Anesthetics. Biophys J. 2015 Nov 17; 109(10):2003-11. PMID: 26588560.
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    17. Ritter DM, Zemel BM, Lepore AC, Covarrubias M. Kv3.4 channel function and dysfunction in nociceptors. Channels (Austin). 2015 Jul 4; 9(4):209-17. PMID: 26039360.
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    18. Woll KA, Weiser BP, Liang Q, Meng T, McKinstry-Wu A, Pinch B, Dailey WP, Gao WD, Covarrubias M, Eckenhoff RG. Role for the propofol hydroxyl in anesthetic protein target molecular recognition. ACS Chem Neurosci. 2015 Jun 17; 6(6):927-35. PMID: 25799399; PMCID: PMC4936777.
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    19. Ritter DM, Zemel BM, Hala TJ, O'Leary ME, Lepore AC, Covarrubias M. Dysregulation of kv3.4 channels in dorsal root Ganglia following spinal cord injury. J Neurosci. 2015 Jan 21; 35(3):1260-73. PMID: 25609640.
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    20. Barber AF, Carnevale V, Klein ML, Eckenhoff RG, Covarrubias M. Modulation of a voltage-gated Na+ channel by sevoflurane involves multiple sites and distinct mechanisms. Proc Natl Acad Sci U S A. 2014 May 6; 111(18):6726-31. PMID: 24753583.
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    21. Covarrubias M. Dipeptidyl-peptidase-like proteins cast in a new role: enabling scorpion toxin block of A-type K+ channels. J Physiol. 2013 May 15; 591(Pt 10):2373-4. PMID: 23678148.
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    22. Fineberg JD, Ritter DM, Covarrubias M. Modeling-independent elucidation of inactivation pathways in recombinant and native A-type Kv channels. J Gen Physiol. 2012 Nov; 140(5):513-27. PMID: 23109714.
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    23. Barber AF, Liang Q, Covarrubias M. Novel Activation of Voltage-gated K+ Channels by Sevoflurane. J Biol Chem. 2012 Nov 23; 287(48):40425-32. PMID: 23038249.
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    24. Zhang J, Qu X, Covarrubias M, Germann MW. Insight into the modulation of Shaw2 Kv channels by general anesthetics: structural and functional studies of S4-S5 linker and S6 C-terminal peptides in micelles by NMR. Biochim Biophys Acta. 2013 Feb; 1828(2):595-601. PMID: 23031574.
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    25. Ritter DM, Ho C, O'Leary ME, Covarrubias M. Modulation of Kv3.4 channel N-type inactivation by protein kinase C shapes the action potential in dorsal root ganglion neurons. J Physiol. 2012 Jan 1; 590(Pt 1):145-61. PMID: 22063632.
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    26. Barber AF, Liang Q, Amaral C, Treptow W, Covarrubias M. Molecular mapping of general anesthetic sites in a voltage-gated ion channel. Biophys J. 2011 Oct 5; 101(7):1613-22. PMID: 21961587.
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    27. Cheng L, Yung A, Covarrubias M, Radice GL. Cortactin is required for N-cadherin regulation of Kv1.5 channel function. J Biol Chem. 2011 Jun 10; 286(23):20478-89. PMID: 21507952.
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    28. Bähring R, Covarrubias M. Mechanisms of closed-state inactivation in voltage-gated ion channels. J Physiol. 2011 Feb 01; 589(Pt 3):461-79. PMID: 21098008; PMCID: PMC3055536.
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    29. Santiago-Castillo JA, Covarrubias M, Sánchez-Rodríguez JE, Perez-Cornejo P, Arreola J. Simulating complex ion channel kinetics with IonChannelLab. Channels (Austin). 2010 Sep-Oct; 4(5):422-8. PMID: 20935453; PMCID: PMC3051876.
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    30. Bhattacharji A, Klett N, Go RC, Covarrubias M. Inhalational anaesthetics and n-alcohols share a site of action in the neuronal Shaw2 Kv channel. Br J Pharmacol. 2010 Apr; 159(7):1475-85. PMID: 20136839.
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    31. Jerng HH, Dougherty K, Covarrubias M, Pfaffinger PJ. A novel N-terminal motif of dipeptidyl peptidase-like proteins produces rapid inactivation of KV4.2 channels by a pore-blocking mechanism. Channels (Austin). 2009 Nov; 3(6):448-61. PMID: 19901547; PMCID: PMC3607289.
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    32. Eckenhoff RG, Xi J, Shimaoka M, Bhattacharji A, Covarrubias M, Dailey WP. Azi-isoflurane, a Photolabel Analog of the Commonly Used Inhaled General Anesthetic Isoflurane. ACS Chem Neurosci. 2010 Feb 17; 1(2):139-145. PMID: 20228895.
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    33. Phuket TR, Covarrubias M. Kv4 Channels Underlie the Subthreshold-Operating A-type K-current in Nociceptive Dorsal Root Ganglion Neurons. Front Mol Neurosci. 2009; 2:3. PMID: 19668710.
      Citations:    
    34. Kaulin YA, De Santiago-Castillo JA, Rocha CA, Nadal MS, Rudy B, Covarrubias M. The dipeptidyl-peptidase-like protein DPP6 determines the unitary conductance of neuronal Kv4.2 channels. J Neurosci. 2009 Mar 11; 29(10):3242-51. PMID: 19279261.
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    35. Dougherty K, Tu L, Deutsch C, Covarrubias M. The dipeptidyl-aminopeptidase-like protein 6 is an integral voltage sensor-interacting beta-subunit of neuronal K(V)4.2 channels. Channels (Austin). 2009 Mar-Apr; 3(2):122-8. PMID: 19372736.
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    36. Schwenk J, Zolles G, Kandias NG, Neubauer I, Kalbacher H, Covarrubias M, Fakler B, Bentrop D. NMR analysis of KChIP4a reveals structural basis for control of surface expression of Kv4 channel complexes. J Biol Chem. 2008 Jul 04; 283(27):18937-46. PMID: 18458082; PMCID: PMC2441559.
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    37. Covarrubias M, Bhattacharji A, De Santiago-Castillo JA, Dougherty K, Kaulin YA, Na-Phuket TR, Wang G. The neuronal Kv4 channel complex. Neurochem Res. 2008 Aug; 33(8):1558-67. PMID: 18357523.
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    38. Dougherty K, De Santiago-Castillo JA, Covarrubias M. Gating charge immobilization in Kv4.2 channels: the basis of closed-state inactivation. J Gen Physiol. 2008 Mar; 131(3):257-73. PMID: 18299396.
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    39. Amarillo Y, De Santiago-Castillo JA, Dougherty K, Maffie J, Kwon E, Covarrubias M, Rudy B. Ternary Kv4.2 channels recapitulate voltage-dependent inactivation kinetics of A-type K+ channels in cerebellar granule neurons. J Physiol. 2008 Apr 15; 586(8):2093-106. PMID: 18276729; PMCID: PMC2465190.
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    40. Rojas P, Garst-Orozco J, Baban B, de Santiago-Castillo JA, Covarrubias M, Salkoff L. Cumulative activation of voltage-dependent KVS-1 potassium channels. J Neurosci. 2008 Jan 16; 28(3):757-65. PMID: 18199775; PMCID: PMC2248284.
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    41. Wang G, Strang C, Pfaffinger PJ, Covarrubias M. Zn2+-dependent redox switch in the intracellular T1-T1 interface of a Kv channel. J Biol Chem. 2007 May 4; 282(18):13637-47. PMID: 17331952.
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    42. Dougherty K, Covarrubias M. A dipeptidyl aminopeptidase-like protein remodels gating charge dynamics in Kv4.2 channels. J Gen Physiol. 2006 Dec; 128(6):745-53. PMID: 17130523.
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    43. Fawcett GL, Santi CM, Butler A, Harris T, Covarrubias M, Salkoff L. Mutant analysis of the Shal (Kv4) voltage-gated fast transient K+ channel in Caenorhabditis elegans. J Biol Chem. 2006 Oct 13; 281(41):30725-35. PMID: 16899454; PMCID: PMC2259281.
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    44. Bhattacharji A, Kaplan B, Harris T, Qu X, Germann MW, Covarrubias M. The concerted contribution of the S4-S5 linker and the S6 segment to the modulation of a Kv channel by 1-alkanols. Mol Pharmacol. 2006 Nov; 70(5):1542-54. PMID: 16887933.
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    45. Wang G, Covarrubias M. Voltage-dependent gating rearrangements in the intracellular T1-T1 interface of a K+ channel. J Gen Physiol. 2006 Apr; 127(4):391-400. PMID: 16533897.
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    46. Wang G, Shahidullah M, Rocha CA, Strang C, Pfaffinger PJ, Covarrubias M. Functionally active t1-t1 interfaces revealed by the accessibility of intracellular thiolate groups in kv4 channels. J Gen Physiol. 2005 Jul; 126(1):55-69. PMID: 15955876.
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    47. Jerng HH, Pfaffinger PJ, Covarrubias M. Molecular physiology and modulation of somatodendritic A-type potassium channels. Mol Cell Neurosci. 2004 Dec; 27(4):343-69. PMID: 15555915.
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    48. Harris T, Graber AR, Covarrubias M. Allosteric modulation of a neuronal K+ channel by 1-alkanols is linked to a key residue in the activation gate. Am J Physiol Cell Physiol. 2003 Oct; 285(4):C788-96. PMID: 12958027.
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    49. Shahidullah M, Harris T, Germann MW, Covarrubias M. Molecular features of an alcohol binding site in a neuronal potassium channel. Biochemistry. 2003 Sep 30; 42(38):11243-52. PMID: 14503874.
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    50. Shahidullah M, Covarrubias M. The link between ion permeation and inactivation gating of Kv4 potassium channels. Biophys J. 2003 Feb; 84(2 Pt 1):928-41. PMID: 12547775.
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    51. Beck EJ, Bowlby M, An WF, Rhodes KJ, Covarrubias M. Remodelling inactivation gating of Kv4 channels by KChIP1, a small-molecular-weight calcium-binding protein. J Physiol. 2002 Feb 1; 538(Pt 3):691-706. PMID: 11826158.
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    52. Holmqvist MH, Cao J, Hernandez-Pineda R, Jacobson MD, Carroll KI, Sung MA, Betty M, Ge P, Gilbride KJ, Brown ME, Jurman ME, Lawson D, Silos-Santiago I, Xie Y, Covarrubias M, Rhodes KJ, Distefano PS, An WF. Elimination of fast inactivation in Kv4 A-type potassium channels by an auxiliary subunit domain. Proc Natl Acad Sci U S A. 2002 Jan 22; 99(2):1035-40. PMID: 11805342; PMCID: PMC117799.
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