Ph.D., University of Miami Medical School, 1982

Research in our laboratory is in the area of molecular and cellular neurobiology, with an emphasis on the function, structure, and regulation of ion channels, and the mechanisms of visual transduction. 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 and 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. These "cyclic nucleotide-gated" ion channels are intimately involved in the first stages of vision, and mutations in these channels cause some forms of blindness (e.g., retinitis pigmentosa).

We study the molecular mechanisms by which these ion channels undergo conformational changes, how they are affected by mutations, and how they are regulated by intracellular factors, such as calcium binding proteins and phosphorylation enzymes, and by external agents such as local anesthetics. Some of our current research centers on the control of ion channel function by the lipid bilayer, by lipophilic modulators and by protein-protein interactions. Our experimental techniques include electrophysiology (mainly patch clamp methods), molecular biology (including site-directed mutagenesis), biochemistry and mathematical/computer modeling. For most projects, we study cloned ion channels heterogously expressed in Xenopus (frog) oocytes, but we also use photoreceptors (rod and cone cells) to study the role of channel modulation in vision. Finally, we study purified ion channel proteins inserted into artificial lipid bilayers

Course director and lecturer in a cell physiology/biophysics course (BI 110) for upper level undergraduates and graduate students. Taught every other spring. Enrollment 30 students (limited enrollment).

Lecturer on general/cellular physiology in a mammalian physiology course (BI 117) for first-year medical students and graduate students. Taught every fall. Enrollment 80 students (limited enrollment).

Lecturer and course director for an introductory physiology course (BI 80) for undergraduates. Taught every other spring, alternately with BI 110. Enrollment about 120-150 students. I also give a few lectures in this course when it is directed by Don Jackson in alternate years.

Guest Lecturer in several other Brown Courses.

Thesis advisor for two Ph.D. students and one honors student; advisor for one postdoctoral research associate and five undergraduate research assistants. Thesis committee member for six Ph.D. students, in addition to my own students.

Cellular physiology and biophysics (BI0110)
Mammalian Physiology (BI0117)
Principles of Physiology (BI0080)

• Horrigan, D.M., Tetreault, M.L., Tsomaia, N., Vasileiou, C., Borhan, B., Mierke, D.F., Crouch, R.K. and Zimmerman, A.L. (2005) "Defining the retinoid binding site in the rod cyclic nucleotide-gated channel." J. Gen. Physiol. 126:453-460. [Full Text/Abstract]
• McCabe, S.L., Pelosi, D.M., Tetreault, M., Miri, A., Nguitragool, W., Kovithvathanaphong, P., Mahajan, R. and Zimmerman, A.L. (2004) "All- trans -retinal is a closed-state inhibitor of rod cyclic nucleotide-gated ion channels". Journal of General Physiology 12: 521-531. [Full Text/Abstract]
• Dean, D.M., Nguitragool, W., Miri, A., McCabe, S.L. and Zimmerman, A.L. (2002) "All- trans -retinal shuts down rod cyclic nucleotide-gated ion channels: a novel role for photoreceptor retinoids in the response to bright light?" Proceedings of the National Academy of Sciences USA 99: 8372-8377. [Full Test/Abstract]
• Zimmerman, A.L. (2002) "Two B or not two B? Questioning the rotational symmetry of tetrameric ion channels". Neuron 36: 997-999. [Full Text/Abstract]
• Crary, J.I., Dean, D.M., Nguitragool, W. and Zimmerman, A.L. (2000) "Mechanism of inhibition of cyclic nucleotide-gated ion channels by diacylglycerol". Journal of General Physiology 116: 755-768. [Full Text/Abstract]
• 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". Journal of General Physiology 116: 769-780. [Full Text/Abstract]
• Zimmerman, A.L. (1995) "Cyclic nucleotide-gated channels". Current Opinion in Neurobiology 5: 296-303. [Abstract]