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| David L. Armstrong, Ph.D., Senior Investigator |
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Dr. Armstrong completed his Ph.D. in Neurophysiology at the California Institute of Technology in 1978. 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 began using 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 Head of the Membrane Signaling Group and Acting Chief of the Laboratory of Neurobiology. Dr. Armstrong's laboratory is studying the regulation of voltage-activated calcium and potassium channels by hormone signaling through G proteins, calcium and reversible protein phosphorylation.
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Staff:
- Christian Erxleben, Ph.D., Senior Research Fellow erxleben@niehs.nih.gov
- Negin Martin, Ph.D., Research Fellow martin12@niehs.nih.gov
- Erica Scappini, Biologist scappinie@niehs.nih.gov
- Jody A. White, Ph.D., Postdoctoral IRTA Fellow whitej2@niehs.nih.gov
- Shilan Wu, Ph.D., Research Fellow wus2@niehs.nih.gov
- Xuying Zhang, Ph.D., Visiting Fellow zhangx3@niehs.nih.gov
Research Interests:
In the Membrane Signaling Group we investigate how ion channel proteins are regulated by signal transduction pathways, particularly the cytoplasmic pathways that involve G proteins, calcium and protein phosphorylation without requiring new gene expression. Many microbial toxins impair human health by disrupting these signaling cascades. Polymorphisms in the genes encoding ion channels also increase human susceptibility to many diseases.
We study voltage-activated calcium and potassium channel proteins at three levels:
- at the molecular level we ask how post-translational changes in structure alter channel protein function recorded with the patch clamp technique;
- at the cellular level we ask how hormones and neuropeptides produce post-translational changes in ion channel structure;
- at the tissue level we are beginning to ask how physiological function is altered by disrupting the signaling pathways and channel regulation with mutations or with environmental toxicants.
We focus on three specific ion channel proteins:
- the dihydropyridine-sensitive, L-type (CaV1.2) calcium channels which are encoded by the CaCNA1C gene and link depolarization to hormone secretion, muscle contraction, and neuronal gene expression;
- the BKca potassium channels, which are encoded by the KCNMA1 gene (slo) and regulate action potential duration in endocrine cells and nerve terminals;
- the Kv11.1-11.3 potassium channels, which are encoded by the ether-a-go-go-related genes, ERG1-3 (KCNH 2, 6 & 7) and regulate action potential frequency in endocrine cells and neurons.
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Selected Recent Publications:
Liao, Y. et al. (2008) Functional interactions among Orai1, TRPCs and STIM1 suggest a STIM-regulated heteromeric Orai/TRPC model for SOCE/Icrac channels, PNAS 105, 2895-2900.
Gentile, S. et al., (2008) The human ERG1 channel polymorphism, K897T, creates a phosphorylation site that inhibits channel activity, Proc. Natl. Acad. Sci. USA 105, 14704-8.
Erxleben, C. et al (2006) Cyclosporin and Timothy syndrome increase mode 2 gating of CaV1.2 calcium channels through aberrant phosphorylation of S6 helices, Proc Natl Acad Sci USA 103, 3932-3937.
Storey, N. M. et al. (2006) Rapid signaling at the plasma membrane by a nuclear receptor for thyroid hormone, Proc Natl Acad Sci USA 103, 5197-5201.
Gentile et al (2006) Rac GTPase signaling through the PP5 protein phosphatase, Proc natl Acad Sci USA 103, 5202-5206.
All Selected Publications
Contact Information:
Dr. David L. Armstrong
Membrane Signaling Section
Laboratory of Neurobiology, NIEHS
111 Alexander Drive
Research Triangle Park, NC 27709-
Telephone: (919) 541-0062 (office),
Email: armstro3@niehs.nih.gov
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