PI: Dr. William Zagotta
Location: University of Washington, Department of Physiology and Biophysics, UW School of Medicine
Conformation dynamics of cyclic nucleotide-regulated ion channels
In response to one or more of a variety of stimuli, including neurotransmitters, voltage, and internal second messengers, ion channels open and allow the passage of certain selected ions across the cell membrane. The long term goal of the Zagotta lab is to determine the molecular mechanisms in ion channels of the opening and closing conformational changes and how they are regulated. We have focused on a family of channels where the opening and closing conformational changes are regulated by the direct binding of cyclic nucleotides, cAMP and cGMP. These channels play a fundamental role in the initial generation of an electrical signal in sensory receptors such as photoreceptors and olfactory receptors,and in the control of the pacemaker activity in cardiac and neuronal cells.To study the mechanism of regulation by cyclic nucleotides, we employ a variety of biophysical approaches including electrophysiology, fluorescence spectroscopy, electron paramagnetic resonance spectroscopy, and X-ray crystallography. By the combination of these approaches we hope to gain new insights into the molecular mechanisms for channel function.