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David Clapham, M.D., Ph.D.

Aldo R. Castaneda Professor of Cardiovascular Research

Children's Hospital
HHMI/ CV Res, Enders 1309
320 Longwood Ave
Boston, MA 02115
Telephone: 617-919-2680
Fax: 617- 731-0787
Email: dclapham@enders.tch.harvard.edu
Predocs: 3 Postdocs: 12 Completed PhD's: 5

 David Clapham

The Clapham laboratory studies signal transduction control of ion channels. One of the chief current areas of research is the cloning, identification, and characterization of TRP channels. The TRP channels are nonselective, 6 transmembrane spanning proteins present in the nervous system and many other cells. In the brain, a group of these channels is activated by G protein (Gq)-linked receptors via the enzyme phospholipase C through an interesting, but poorly understood sequence of steps. The channels depolarize neurons as well as bring calcium into cells. We have recently cloned and characterized a novel member of this class of channels that contains a kinase domain within it carboxy terminal tail. This channel may be involved in the control of cell division, but the receptors that activate the channel, and how they activate the channel, remain a mystery.

A second major area of interest is in the G protein gated inwardly rectifying class of ion channels. The GIRK channels slow firing rates of excitable cells by hyperpolarizing the membrane potential. At least eight neurotransmitters in the central nervous system activate this type of ion channel through direct release of calcium from the heterotrimeric G protein complex to directly activate the GIRK channel. We are most interested in how the calcium protein gates the channel complex. We have also generated several knockout mouse models to study the role of GIRK channels in functions as diverse as learning and pain.

 

References:

  • Wickman, K, Karschin, C, Karschin, K, Picciotto, MR, and Clapham, DE. Brain localization and behavioral impact of the G-protein-gated K+ channel subunit GIRK4. Journal of Neuroscience, 2000, 20: 5608-5615.
  • Runnels, LW, Yue, L, and Clapham, DE. TRP-PLIK, a bifunctional protein with kinase and ion channel activities. Science. 2001, 291, 1043-1046.
  • Strübing, C, Krapivinsky, G, Krapivinsky, L and Clapham, DE. TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron. 2001. 29, 645-655.
  • Yue, L, Peng, J-B. Hediger, MA, and Clapham, DE. CaT1 Manifests the Pore Properties of the Calcium Release Activated Calcium Channel (ICRAC). Nature, 2001, 410, 705-709