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Membrane Signaling Group

Regulation of Ion Channel Proteins

David L. Armstrong, Ph.D.
David L. Armstrong, Ph.D.
Principal Investigator

Tel (919) 541-0062
Fax (919) 541-4611
P.O. Box 12233
Mail Drop F2-05
Research Triangle Park, North Carolina 27709
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Research Summary

The Membrane Signaling Group (MSG) studies the regulation of ion channel proteins by hormonal signaling through G proteins, calcium and protein phosphorylation.

The figure depicts a single hERG ion channel protein in the surface membrane under two conditions: phosphorylated and dephosphorylated. The consequences of phosphorylation on channel activity and cell excitability are depicted underneath. The phosphorylated channel closes quickly and results in more frequent electrical spikes. In contrast, the dephosphorylated channel closes more slowly and delays the onset of subsequent spikes.

Many environmental toxicants impair human health by disrupting these signaling cascades. Mutations in the genes encoding ion channels also increase human susceptibility to many diseases. The MSG focuses on the voltage-activated channels that are selectively permeable to calcium or to potassium and uses the patch clamp technique to study channel protein function and regulation at the molecular level in live cells in real time. The work is being continued at three levels of biological organization. At the molecular level, the group studies the structural basis of channel regulation by protein phosphorylation. At the cellular level, the ion channels are being used as a quantitative assay system to investigate the mechanisms linking G proteins to the protein kinases and phosphatases which regulate channel activity. Finally, at the physiological level the group has begun to explore the significance of the signaling pathways for neuronal development, function, and survival. The goal of the Membrane Signaling Group is to determine how disruption of these signal transduction pathways by pathogens and environmental toxicants contributes to the degenerative diseases which increasingly debilitate our aging population.

Major areas of research:

  • Ion channel regulation by G protein signaling, calcium and phosphorylation
  • Protein phosphatase regulation by hormones and toxicants
  • Thyroid hormone signaling

Current projects:

  • CaV1.2 channel regulation by calcium-dependent kinases and phosphatases
  • KCNMA1 channel regulation by ethanol
  • KCNH2 regulation by Rho GTPases
  • Thyroid hormone receptor signaling through phosphoinositide 3 kinase

David L. Armstrong, Ph.D., is Acting Chief of the Laboratory of Neurobiology and head of the Membrane Signaling Group. Armstrong was trained in neurophysiology at the California Institute of Technology and received his Ph.D. in 1978. Following postdoctoral research at University College London, the Salk Institute and the University of California in Los Angeles, Armstrong joined the intramural research program within NIEHS as Head of the Membrane Signaling Group in 1987. He became a tenured Research Physiologist in 1994.

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Last Reviewed: August 22, 2007