Manuel Covarrubias, MD, Ph.D.

Contact Dr. Covarrubias

900 Walnut St., Suite 400

Philadelphia, PA 19107

(215)-503-4341
(215)-955-4949 fax

Graduate School
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO

University Appointment
Professor (2004)

Research and Clinical Interests
The research in my laboratory focuses on voltage-gated potassium channels (Kv channels) expressed in the nervous system and the heart. We investigate the molecular mechanisms governing the function and regulation of these ion channels. In particular, we focus on: 1) inactivation gating of Kv channels and its modulation by auxiliary subunits and signaling cascades; 2) structural mapping of inhaled anesthetic/alcohol sites; and 3) functional impact of A-type potassium currents in dorsal root ganglion neurons. These studies can impact our understanding of neuronal plasticity, epilepsy, pain, autism, arrhythmias, anesthesia and alcohol intoxication. Furthermore, they may reveal potential drug-targets. The research platform of our work is based on a modern multidisciplinary approach, which combines electrophysiology, molecular biology, biochemistry, pharmacology and mathematical modeling.

Publications

Most recent Peer-reviewed Publications

1. 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
2. Modeling-independent elucidation of inactivation pathways in recombinant and native A-type Kv channels
3. Novel activation of voltage-gated K+ channels by sevoflurane
4. Modulation of Kv3.4 channel N-type inactivation by protein kinase C shapes the action potential in dorsal root ganglion neurons
5. Molecular mapping of general anesthetic sites in a voltage-gated ion channel
6. Cortactin is required for N-cadherin regulation of Kv1.5 channel function
7. Mechanisms of closed-state inactivation in voltage-gated ion channels
8. Alcohol and anesthetic action at the gate of a voltage-dependent K+ channel
9. Molecular physiology and modulation of somatodendritic A-type potassium channels
10. Allosteric modulation of a neuronal K+ channel by 1-alkanols is linked to a key residue in the activation gate
11. Molecular features of an alcohol binding site in a neuronal potassium channel
12. The link between ion permeation and inactivation gating of Kv4 potassium channels
13. Remodelling inactivation gating of Kv4 channels by KChIP1, a small-molecular-weight calcium-binding protein
14. Elimination of fast inactivation in Kv4 A-type potassium channels by an auxiliary subunit domain
15. Kv4 channels exhibit modulation of closed-state inactivation in inside-out patches
16. Potent inhibition of the aortic smooth muscle maxi-K channel by clinical doses of ethanol
17. General anesthetic action at an internal protein site involving the S4- S5 cytoplasmic loop of a neuronal K+ channel
18. Inactivation gating of Kv4 potassium channels: Molecular interactions involving the inner vestibule of the pore
19. Injection of Xenopus oocytes with mRNA from cultured neurons induces new currents and susceptibility to the damaging action of ruthenium red
20. Receptor-coupled regulation of K+ channel N-type inactivation

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