Research Topics
| Zhe LuSummaryAffiliation: University of Pennsylvania Country: USA Publications
Research Grants
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Detail Information
Publications
Kinetics of inward-rectifier K+ channel block by quaternary alkylammonium ions. dimension and properties of the inner poreD Guo
Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Gen Physiol 117:395-406. 2001..These observations argue that between the intracellular solution and the QA-binding locus, there exists a constricted pathway, whose dimension ( approximately 9 A) is comparable to that of a K+ ion with a single H2O shell...- Mechanism of rectification in inward-rectifier K+ channelsZhe Lu
Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Annu Rev Physiol 66:103-29. 2004.... - Ion conduction pore is conserved among potassium channelsZ Lu
Department of Physiology, University of Pennsylvania, Philadelphia 19104, USA
Nature 413:809-13. 2001..The resulting chimaeras retain the respective functional hallmarks of the eukaryotic channels, which indicates that the ion conduction pore is indeed conserved among K+ channels... - Interaction mechanisms between polyamines and IRK1 inward rectifier K+ channelsDonglin Guo
University of Pennsylvania, Department of Physiology D302A Richards Building, 3700 Hamilton Walk, Philadelphia, PA 19104, USA
J Gen Physiol 122:485-500. 2003..Thus, nature has optimized not only the blocker but also, in a complementary manner, the channel for producing rapid, high-affinity, and strongly voltage-dependent channel block, giving rise to exceedingly sharp rectification... - Coupling between voltage sensors and activation gate in voltage-gated K+ channelsZhe Lu
Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USA
J Gen Physiol 120:663-76. 2002..One sequence is the so called S4-S5 linker distal to the voltage-sensing S4, while the other is around the COOH-terminal end of S6, a region containing the actual gate-forming residues... - Mechanism of rectification in inward-rectifier K+ channelsDonglin Guo
Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USA
J Gen Physiol 121:261-75. 2003.... - Evidence for sequential ion-binding loci along the inner pore of the IRK1 inward-rectifier K+ channelHyeon-Gyu Shin
Department of Physiology, University of Pennsylvasnia, 3700 Hamilton Walk, Philadelphia, PA 19104, USA
J Gen Physiol 126:123-35. 2005.... - Removal of phospho-head groups of membrane lipids immobilizes voltage sensors of K+ channelsYanping Xu
Department of Physiology, University of Pennsylvania, 3700 Hamilton Walk, Philadelphia, Pennsylvania 19104, USA
Nature 451:826-9. 2008.... - Characterization of inward-rectifier K+ channel inhibition by antiarrhythmic piperazineYanping Xu
Department of Physiology, University of Pennsylvania, 3700 Hamilton Walk, Philadelphia, Pennsylvania 19104, USA
Biochemistry 43:15577-83. 2004..We also examine the channel selectivity of piperazine and its molecular determinants... - Extracellular protons titrate voltage gating of a ligand-gated ion channelJuan Ramón Martínez-François
Department of Physiology, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
J Gen Physiol 136:179-87. 2010..Consequently, at low extracellular pH the channels become practically fully voltage gated, even in the presence of a saturating concentration of cGMP... - Enzymatic activation of voltage-gated potassium channelsYajamana Ramu
Department of Physiology, University of Pennsylvania, 3700 Hamilton Walk, Philadelphia, Pennsylvania 19104, USA
Nature 442:696-9. 2006..Here we report the apparent activation of voltage-gated K+ (Kv) channels by a sphingomyelinase... - Mechanism of the voltage sensitivity of IRK1 inward-rectifier K+ channel block by the polyamine spermineHyeon Gyu Shin
Department of Physiology, University of Pennsylvania, Philadelphia 19104, USA
J Gen Physiol 125:413-26. 2005.... - Mutations reveal voltage gating of CNGA1 channels in saturating cGMPJuan Ramón Martínez-François
Department of Physiology, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
J Gen Physiol 134:151-64. 2009.... - Physical determinants of strong voltage sensitivity of K(+) channel blockYanping Xu
Department of Physiology, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Nat Struct Mol Biol 16:1252-8. 2009..This heretofore unrecognized 'gasket' ensures that the blocker can effectively displace K(+) ions across the selectivity filter to generate exceedingly strong voltage sensitivity... - Short variable sequence acquired in evolution enables selective inhibition of various inward-rectifier K+ channelsYajamana Ramu
Department of Physiology, University of Pennsylvania, 3700 Hamilton Walk, Philadelphia, Pennsylvania 19104, USA
Biochemistry 43:10701-9. 2004..Finally we show that, in the heteromeric GIRK1/4 channels, the GIRK4 and not GIRK1 subunit confers the high affinity for TPN... - Engineered specific and high-affinity inhibitor for a subtype of inward-rectifier K+ channelsYajamana Ramu
Department of Physiology, University of Pennsylvania, 3700 Hamilton Walk, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 105:10774-8. 2008..This success not only yields a highly desirable tool but, perhaps more importantly, demonstrates the practical feasibility of engineering subtype-specific K(+) channel inhibitors... - Intrinsic versus extrinsic voltage sensitivity of blocker interaction with an ion channel poreJuan Ramón Martínez-François
Department of Physiology, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
J Gen Physiol 135:149-67. 2010.... - Inhibition of CFTR Cl- channel function caused by enzymatic hydrolysis of sphingomyelinYajamana Ramu
Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 104:6448-53. 2007.... - Blockade of a retinal cGMP-gated channel by polyaminesZ Lu
Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104
J Gen Physiol 113:35-43. 1999..Blockade of the CNG channel by polyamines may play an important role in suppressing noise in the signal transduction system in rods... - Titration of tertiapin-Q inhibition of ROMK1 channels by extracellular protonsY Ramu
Department of Physiology, University of Pennsylvania, Philadelphia 19104, USA
Biochemistry 40:3601-5. 2001..This derivative-denoted tertiapin-KQ (TPN(KQ))-not only is practically insensitive to extracellular pH but also binds to the channel with even higher affinity than TPN(Q) at extracellular pH 7.6... - The antioxidant role of thiocyanate in the pathogenesis of cystic fibrosis and other inflammation-related diseasesYanping Xu
Department of Physiology, Howard Hughes Medical Institute, University of Pennsylvania, 3700 Hamilton Walk, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 106:20515-9. 2009.... - IRK1 inward rectifier K(+) channels exhibit no intrinsic rectificationDonglin Guo
Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USA
J Gen Physiol 120:539-51. 2002..Furthermore, our study helps define the optimal experimental conditions for studying IRK1... - A shaker K+ channel with a miniature engineered voltage sensorYanping Xu
Department of Physiology, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
Cell 142:580-9. 2010..Our study also shows that the hydrophobic residues between the voltage-sensing arginines help set the sensor's characteristic chemical equilibrium between activated and deactivated states... - Apo and InsP?-bound crystal structures of the ligand-binding domain of an InsP? receptorChun Chi Lin
Department of Physiology, Howard Hughes Medical Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Nat Struct Mol Biol 18:1172-4. 2011..Whereas apo LBD may spontaneously transition between gating conformations, InsP(3) binding shifts this equilibrium toward the active state... - Synthesis and study of alendronate derivatives as potential prodrugs of alendronate sodium for the treatment of low bone density and osteoporosisPetr Vachal
Department of Basic Chemistry, Merck Research Laboratories, Merck and Co, Rahway, New Jersey 07065, USA
J Med Chem 49:3060-3. 2006..Pharmacokinetic studies of N-myristoylalendronic acid revealed that 25% have been converted in vivo after i.v. administration in rat, providing an important proof-of-concept for this strategy...
Research Grants
- MECHANISMS OF PERMEATION IN INWARD RECTIFIER K+ CHANNELSZhe Lu; Fiscal Year: 2007..They represent therefore important pharmacological targets for medical intervention in various disease states. ..
- MECHANISMS OF PERMEATION IN INWARD RECTIFIER K+ CHANNELSZhe Lu; Fiscal Year: 2009..They represent therefore important pharmacological targets for medical intervention in various disease states. ..
- MECHANISMS OF PERMEATION IN INWARD RECTIFIER K+ CHANNELSZhe Lu; Fiscal Year: 2010..They represent therefore important pharmacological targets for medical intervention in various disease states. ..
- Permeation of Inward Rectifier K+ ChannelsZhe Lu; Fiscal Year: 2006..Thus, these channels represent important pharmacological targets for medical intervention during various disease states. ..
- Development and study of specific Kir channel inhibitorsZhe Lu; Fiscal Year: 2007..1. The outcome of the proposed studies will significantly enhance our ability to decipher the physiological functions of Kir channels in a given cell type or tissue, and help in the development of effective therapeutic agents. ..
- Development and study of specific Kir channel inhibitorsZhe Lu; Fiscal Year: 2009..abstract_text> ..
- Development /use of peptidic inhibitors for Kir channelsZhe Lu; Fiscal Year: 2004..The inhibitors that we develop will be powerful tools both for investigating the physiology and/or pathophysiology of the channels and for developing drugs that specifically target these channels. ..
- MECHANISMS OF PERMEATION IN INWARD-RECTIFIER K+ CHANNELSZhe Lu; Fiscal Year: 2001..The proposal investigates the mechanisms rectification and the interactions of specific polyamines with rectifying channels. ..
- MECHANISMS OF PERMEATION IN INWARD RECTIFIER K+ CHANNELSZhe Lu; Fiscal Year: 2002..For example, G-protein gated inward-rectifier K+ channels mediate the regulation of heart rate by vagal nerve, and ATP-sensitive inward-rectifier K+ channels are important during cardiac ischemia. (End of Abstract) ..