Associate Professor
Office: VBR 375
E-Mail: varnum@vetmed.wsu.edu
Phone: (509) 335-0661
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.
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 IPN 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)
PubMed Publications (Note: PubMed Search may produce additional "Varnum"
authors.)
