David L. Armstrong

生物谷

Dr. Armstrong received his B.A. in 1972 from the University of Oregon in Eugene and his Ph.D. from the California Institute of Technology in 1979. His graduate studies in the laboratory of Henry Lester focused on the kinetics of tubocurare action at the frog nerve-muscle synapse. As a postdoctoral fellow at University College, London, and the Salk Institute, Dr. Armstrong studied the role of gap junctions in skeletal muscle development and their regulation by neuromuscular activity. In 1984, he joined Roger Eckert's laboratory in the Biology Department at the University of California, Los Angeles, where he developed rat pituitary cell lines as model systems for patch clamp studies of ion channel regulation by signal transduction pathways. Dr. Armstrong joined the intramural research program within the NIEHS in 1987, where he is currently a Senior Investigator and Head of the Membrane Signaling Group within the Laboratory of Signal Transduction. He is also Chair of the Intramural Faculty of Environmental Neuroscience. Dr. Armstrong's laboratory is studying the regulation of potassium channels by neuropeptide receptors, with emphasis on pathways involving protein phosphatases.

Photo of David L. Armstrong, Ph.D., Senior Investigator

Research Interests:

In the Membrane Signaling Group (http://dir.niehs.nih.gov/dirlst/ groups/armstrong.htm), we study the signal transduction pathways that regulate cell function without altering gene expression. Ion channel proteins are the effectors for many of these pathways, regulating electrical signaling in nerve cells, hormone secretion from endocrine cells, contractility of cardiac and vascular muscle cells, fluid transport across epithelial cells, and cell fate and migration in immune cells. In view of the many human diseases which result from inherited mutations in ion channel genes, it is expected that environmental toxicants which disrupt the regulation of those channels will have similar consequences for human health.

We focus on the voltage-dependent channels that are selectively permeable to calcium or to potassium. The patch clamp technique allows us to study ion channel proteins at the molecular level in live cells. We are particularly interested in the signaling pathways linking G protein coupled receptors to ion channel regulation through calcium and reversible protein phosphorylation. We have recently discovered two novel signaling pathways controlling ion channels through Rho family GTPases in the mammalian neuroendocrine system (Storey et al. 2002). Disruption of these novel signaling cascades is postulated to contribute to several specific human neurological diseases.

An increasing number of microbial toxins and industrial xenobiotics are being identified as potent and selective inhibitors of cell communication in the nervous system. By disrupting the action of neuropeptides on cells of the cardiovascular, endocrine and immune systems, environmental toxicants also impair the body's responses to stress and infection. Intramural research at NIEHS is directed to identifying the basic cellular and molecular mechansims which determine susceptibility of the human nervous system to environmental toxicants during development, maturation, and aging.

Selected Recent Publications:

Tian L, Coghill LS, MacDonald SH, Armstrong DL, Shipston MJ (2003) Leucine zipper domain targets PKA to mammalian BK channels, Journal of Biological Chemistry 278 (10), 8669-8677.
Erxleben C, Gomez-Alegria C, Darden T, Mori Y, Birnbaumer L, Armstrong DL (2003) Modulation of cardiac CaV1.2 channels by dihydropyridine and phosphatase inhibitor requires Ser-1142 in the domain III pore loop, Proc. Natl. Acad. Sci. USA 100 (5), 2929-2934.
Erxleben C, Everhart AL, Romeo C, Florance H, Bauer MB, Alcorta DA, Rossie S, Shipston MJ, Armstrong DL (2002) Interacting effects of N-terminal variation and strex exon splicing on slo potassium channel regulation by calcium, phosphorylation, and oxidation, Journal of Biological Chemistry 277 (30), 27045-27052.
N.M. Storey, J.P. O'Bryan & D.L. Armstrong (2002) Rac and Rho mediate opposing hormonal regulation of ether-a-go-go related potassium channels, Current Biology 12 (1), 27-33.
Hall, S.K. & Armstrong, D.L. (2000) Conditional and unconditional inhibition of calcium-activated potassium channels by reversible protein phosphorylation, J. Biol. Chem. 275 (6), 3749 - 3754.

Contact Information:

Dr. David L. Armstrong
Membrane Signaling Section
Laboratory of Signal Transduction, NIEHS
111 Alexander Drive
Research Triangle Park, NC 27709-

Telephone: (919) 541-0062 (office),
Email: armstro3@niehs.nih.gov