报告人：王广宇 Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College of Thomas Jefferson University 题目：  Molecular switch coupling between cell signaling and electric activity via a voltage-gated potassium channel 时间：   10:30 am, 18 July 2007 地点：   生化楼2层224生物物理会议室     Molecular switch coupling between cell signaling and electric activity via a voltage-gated potassium channel   The intracellular T1 domain of most eukaryotic Kv channels exists as a “hanging-gondola” below the transmembrane regions and is a multi-masking center determining subfamily specific assembly, docking of auxiliary subunits and gating.   The gating role of the T1 domain is puzzling because the membrane spanning regions that constitute the Kv channel core directly control voltage-dependent gating and K +-selective permeation.  However, our studies show that the T1-T1 intersubunit interface undergoes a conformational change coupled to voltage-dependent gating.  In intact Kv4 channels, restriction of this conformational change by sulfhydryl modification of specific T1 Zn++ site cysteines hinders activation and thus the T1 Zn++ site is an attractive target for redox modulation.  Internal nitric oxide (NO) inhibits channel activity profoundly by forming a disulfide bond between C110 from one subunit and C132 from the neighboring subunit.  Inhibition is reversed by reduced glutathione and suppressed by intracellular Zn++.  Further studies suggest that intra-subunit Zn++ coordination involving H104, C131 and C132 protects against the formation of the inhibitory disulfide bond.  Therefore, the interfacial T1 Zn++ site of Kv4 channels acts as a Zn++-dependent redox switch that may regulate the activity of neuronal and cardiac A-type K+ currents under physiological and pathological conditions. 欢迎光临！
Biosketch   My name is Guangyu Wang with expertise in chemistry, biophysics and electrophysiology.  I earned B.S in Radiochemistry in 1989 from Lanzhou University.  Two years later I came to Institute of Biophysics, Chinese Academy of Sciences to pursue my graduate education and got M.S in Biophysics in 1994.   Since then I had studied traditional Chinese medicine in Chinese Academy of Somatic Sciences for three years.  To bridge Chinese medicine with modern life science, I returned to Institute of Biophysics to study bioenergy.  In 1999 I was supported to finish my PhD training in electric-optical measurements in Max-Planck-Institute for Biophysical Chemistry, Germany.  One year later I got my Ph.D and began my postdoctoral training in electrophysiology in Oregon Health and Sciences University and Thomas Jefferson University, USA.  Up to now I have published more than twenty peer-reviewed papers.  I am also an active member of Biophysical Society and Society of General Physiologists.  My major research interest focuses on the molecular switch coupling between physical signals and chemical signals in biological systems or organisms, switch-based drug or probe design and optical biosensors.    (179 words)