Michael Varnum, Ph.D. of the Department of VCAPP in the College of Veterinary Medicine at Washington State University

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Michael Varnum, Ph.D.

Assistant Professor

E-Mail: varnum@vetmed.wsu.edu

Phone: (509) 335-0701

The primary focus of the Varnum laboratory is to investigate the molecular mechanisms of ion channels that are directly activated by intracellular cyclic nucleotides. Cyclic nucleotide-gated (CNG) channels are best characterized for the role they play in photoreceptor cells of the vertebrate retina and in olfactory sensory neurons. They convert a chemical signal (a change in cyclic nucleotide concentration) into an electrical signal that is ultimately used by the brain in processing sensory information.

The laboratory applies a diverse set of techniques to study these proteins, including molecular biology, biochemistry, genetics, and electrophysiology.

Recently, Dr. Varnum has determined the amino acid residues responsible for the profound selectivity of the retinal channel for cGMP. Dr. Varnum has also characterized interdomain interactions in olfactory CNG channels that underlie the regulation of these channels by Ca2+-calmodulin and the adaptation of olfactory sensory neurons to prolonged exposure to odorants. Current experiments are directed toward understanding the conformational changes and protein-protein interactions responsible for the assembly, activation and regulation of CNG channels. In addition, the Varnum laboratory is interested in determining the functional basis for identified retinal diseases that have been linked to mutations in CNG channel genes. These studies will provide insight into the signaling properties of several sensory and non-sensory systems.

Michael Varnum

Biographical Information

Mike Varnum received his B.S. in Microbiology and Immunology (1983) from the University of Washington. He earned his Ph.D. from the Vollum Institute and Department of Cell Biology and Anatomy (1994) at Oregon Health Sciences University in Portland, Oregon. He lectured in biophysics and cell physiology from 1995-97 at the University of Washington, and was a Research Associate at the Howard Hughes Medical Institute at the University of Washington from 1994-98. In 1998, Dr. Varnum joined the Department of VCAPP as an assistant professor.

Selected Publications

Varnum, M.D., K.D. Black, and W.N. Zagotta. Molecular mechanism for ligand discrimination of cyclic nucleotide-gated channels. Neuron 15:619-625, 1995.

Varnum, M.D., and W.N. Zagotta. Interdomain interactions underlying activation of cyclic nucleotide-gated channels. Science 278:110-113, 1997.

Peng, C., E.D. Rich, C.A. Thor, and M.D. Varnum. Functionally important calmodulin binding sites in both N- and C-terminal regions of the cone photoreceptor cyclic nucleotide-gated channel CNGB3 subunit. J. Biol. Chem. 278:24617-24623, 2003.

Zheng, J., M.D. Varnum and W.N. Zagotta. Disruption of an intersubunit interaction underlies Ca²⁺-calmodulin modulation of cyclic nucleotide-gated channels. J. Neuroscience. 21:8167-8175, 2003.

Peng, C., E.D. Rich, and M.D. Varnum. Achromatopsia-associated mutation in the cone photoreceptor cyclic nucleotide gated channel CNGB3 subunit alters the ligand sensitivity and pore properties of heteromeric channels. J. Biol. Chem. 278:34533-34540, 2003.

Peng, C., E.D. Rich, and M.D. Varnum. Subunit configuration of heteromeric cone cyclic nucleotide-gated channels. Neuron (in press)

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