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Molecular Neurophysiology Unit
Miguel Holmgren, Ph.D., Investigator
Dr. Holmgren received his B.S in 1985 from Universidad Autonoma Metropolitana, Unidad Xochimilco, Ciudad de Mexico. In 1994 he received his Ph.D. in Physiology and Biophysics from Finch University of Health Sciences within the Chicago Medical School, working on the sodium/potassium ATPase with Robert Rakowski. Dr. Holmgren went on to do postdoctoral training with Gary Yellen at Harvard Medical School where he studied the gating mechanisms of voltage-activated potassium channels. He joined the NINDS as an Investigator in 2001. Dr. Holmgren's laboratory is exploring the structure and biophysics of various ion channels and transporters.
Staff:
- Jin Chen, Ph.D., Postdoctoral Fellow, 301-451-6258 chenjin2@ninds.nih.gov
- Jorge Contreras, Ph.D., Research Fellow, 301-451-6257 contrerjo@ninds.nih.gov
- Carlos Gonzalez, Ph.D., Postdoctoral Fellow, 301-451-6257 gonzalezca@ninds.nih.gov
- Angelica Maria Lopez, Ph.D., Visiting Fellow, 301-451-6258 lopezang@ninds.nih.gov
- Van K Nguyen, B.S., Predoctoral IRTA Fellow, 301-451-6258 nguyenvan@ninds.nih.gov
- Francisco Palma, M.Sc, Predoctoral Fellow palmaf@ninds.nih.gov
- Deepa Srikumar, M.Sc, Research Assistant, 301-451-6258 srikumad@ninds.nih.gov
Research Interests:
Neurons contain a variety of membrane proteins responsible for the continuous traffic of ions and molecules across the cell membrane. Our main goal is to understand how ions are transported through some of these proteins. We are presently interested in ion channels and the sodium/potassium ATPase; the former moving ions at rates near diffusion, while the latter at rates of about 100 per sec. For both types of proteins, we are asking similar questions. How do ions access their pathway? Which regions of the proteins form the permeation pathways that allow ions to move across the membrane? How does the protein regulate the traffic of ions? What are the interactions of molecules like blockers and toxins with these proteins? We attempt to answer these types of questions by combining molecular biology, chemical modification and electrophysiological techniques.
Recently, we have become increasingly interested in understanding how RNA editing alters the function of membrane proteins. RNA editing is a post-transcriptional modification believed to be a major mechanism in acclimatization and/or adaptation. An enzyme converts adenosine into inosine, which is interpreted as guanosine by the cellular machinery. This conversion provides a vast mutagenic repertoire by which critical positions in a protein can be altered. Although, a growing number of mRNA substrates have been shown to be edited, very little is known about the functional consequences of these modifications. We are taking advantage of the apparent high levels of editing in squid to examine RNA editing in a variety of membrane proteins including ion channels and transporters. Studying the regulation of membrane proteins by RNA editing will reveal how nature functionally tunes these proteins, and guide our questions on the structure and function of these important cellular machines.
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Selected Publications:
- Contreras, J.E. Srikumar, D. and Holmgren, M. (2008) Gating at the selectivity filter in cyclic nucleotide-gated channels, PNAS 105, 3310-3314. Full Text/Abstract
- Colina, C., J.J.C. Rosenthal, J.A. DeGiorgis, D. Srikumar, N. Iruku& M. Holmgren (2007) Structural basis of Na+/K+-ATPase adaptation to marine environments, Nature Structural Molecular Biology 14, 427-431. Full Text/Abstract
- Holmgren, M. and Rakowski, RF. (2006) Charge Translocation by the Na+/K+ Pump under Na+/Na+ Exchange Conditions: Intracellular Na+ Dependence, Biophys. J. 90, 1607-16. Full Text/Abstract
- Contreras, JE and Holmgren, M. (2006) Access of quaternary ammonium blockers to the internal pore of cyclic nucleotide-gated channels: implications for the location of the gate., J. Gen. Physiol. 127, 481-94. Full Text/Abstract
- Bhalla, T., Rosenthal, JJC, Holmgren, M., and Reenan, R. (2004) Control of Human Potassium Channel Inactivation by Editing of a Small mRNA Hairpin, Nature Structural & Molecular Biology 11, 950-956. Full Text/Abstract
- Soler-Llavina GJ, Holmgren M, and Swartz KJ (2003) Defining the Conductance of the Closed State in a Voltage-Gated K+ Channel, Neuron 38, 61-67. Full Text/Abstract
- Holmgren, Miguel (2003) Influence of Permeant Ions on Gating in Cyclic Nucleotide-gated Channels, J. Gen Physiol 121, 61-72. Full Text/Abstract
All Selected Publications
Contact Information:
Dr. Miguel Holmgren
Molecular Neurophysiology Unit, NINDS
Porter Neuroscience Research Center
Building 35 Room 3B-1016
35 Convent Drive, MSC 3701
Bethesda, MD 20892-3701
Telephone: 301-451-6259 office,
301-451-6258 laboratory,
301-480-3943 fax
Email: holmgren@ninds.nih.gov
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