Ph.D., University of Miami Medical School
Professor
Department of Molecular Pharmacology, Physiology and Biotechnology
327 Biomedical Center
Tel: (401) 863-2224
Email: Anita_Zimmerman@Brown.edu
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Research in our laboratory is in the area of molecular & cellular neurobiology, with an emphasis on the function, structure and regulation of ion channels. Essentially every function in the body is controlled by the activity of ion channels -- membrane proteins that change their conformation in response to chemical and electrical signals, allowing specific ions to enter or exit cells as needed. Ion channels are critically involved in functions as diverse as nerve impulses in the brain, the beating of the heart, visual perception, muscle contraction, learning and memory, and embryonic development. They are also the targets of many drugs, such as those used to treat pain and heart disease, and genetic defects in ion channels can cause devastating diseases, such as cystic fibrosis. Our current work centers on ion channels that are opened by direct interaction with cyclic nucleotides (e.g., cyclic AMP & cyclic GMP) and by changes in membrane voltage. Since these ion channels contain pores that allow the passage of Ca2+ and Na+ into cells, their activity affects membrane voltage and the intracellular concentration of Ca2+, both of which are vital regulators of cell function. We study the molecular mechanisms by which these channels undergo conformational changes and are regulated by intracellular factors, such as diacylglycerol, calmodulin and phosphorylation enzymes, as well as by external agents such as local anesthetics. Much of our current research centers on the control of ion channel function by the lipid bilayer and by lipophilic modulators. Our experimental techniques include patch clamp electrophysiological methods, molecular biology (including site-directed mutagenesis) and computational studies. For most projects, we study cloned channels heterogously expressed in Xenopus (frog) oocytes.

Zimmerman, A.L. (1995) Cyclic nucleotide-gated channels. Current Opinion in Neurobiology 5: 296-303.

Gordon, S.E., Downing-Park, J. and Zimmerman, A.L. (1995) Modulation of the cGMP-gated ion channel in frog rods by calmodulin and an endogenous inhibitory factor. J. Physiol. 486: 533-546.

Crary, J.I., Dean, D.M., Nguitragool, W. and Zimmerman, A.L. (2000) Mechanism of inhibition of cyclic nucleotide-gated ion channels by diacylglycerol. J. Gen. Physiol. 116: 755-768.

Crary, J.I., Dean, D.M., Maroof, F. and Zimmerman, A.L. (2000) Mutation of a single residue in the S2-S3 loop of CNG channels alters the gating properties and sensitivity to inhibitors. J. Gen. Physiol. 116: 769-780.