M Pusch

Summary

Affiliation: Via De Marini
Country: Italy

Publications

  1. pmc Conformational changes in the pore of CLC-0
    Alessio Accardi
    Istituto di Biofisica, Sezione di Genova, CNR, I 16149 Genova, Italy
    J Gen Physiol 122:277-93. 2003
  2. pmc Gating and flickery block differentially affected by rubidium in homomeric KCNQ1 and heteromeric KCNQ1/KCNE1 potassium channels
    M Pusch
    Istituto di Cibernetica e Biofisica, Consiglio Nazionale della Ricerche, Via De Marini 6, I 16149 Genova, Italy
    Biophys J 78:211-26. 2000
  3. ncbi Myotonia caused by mutations in the muscle chloride channel gene CLCN1
    Michael Pusch
    Istituto di Cibernetica e Biofisica, CNR, Genova, Italy
    Hum Mutat 19:423-34. 2002
  4. pmc Mechanism of block of single protopores of the Torpedo chloride channel ClC-0 by 2-(p-chlorophenoxy)butyric acid (CPB)
    M Pusch
    Istituto di Cibernetica e Biofisica, Consiglio Nazionale delle Ricerche, I 6149 Genova, Italy
    J Gen Physiol 118:45-62. 2001
  5. pmc Two open states and rate-limiting gating steps revealed by intracellular Na+ block of human KCNQ1 and KCNQ1/KCNE1 K+ channels
    M Pusch
    Istituto di Cibernetica e Biofisica, CNR, Via De Marini 6, I 16149 Genova, Italy
    J Physiol 533:135-43. 2001
  6. ncbi Pharmacological characterization of chloride channels belonging to the ClC family by the use of chiral clofibric acid derivatives
    M Pusch
    Istituto di Cibernetica e Biofisica, CNR, Genova, Universita di Bari, Bari, Italy
    Mol Pharmacol 58:498-507. 2000
  7. pmc Chloride dependence of hyperpolarization-activated chloride channel gates
    M Pusch
    Centre for Molecular Neurobiology ZMNH, University of Hamburg, Hamburg, Germany
    J Physiol 515:341-53. 1999
  8. ncbi Increase of the single-channel conductance of KvLQT1 potassium channels induced by the association with minK
    M Pusch
    Istituto di Cibernetica e Biofisica, CNR, Via De Marini 6, I 16149 Genova, Italy
    Pflugers Arch 437:172-4. 1998
  9. pmc Identification of sites responsible for the potentiating effect of niflumic acid on ClC-Ka kidney chloride channels
    G Zifarelli
    Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Genova, Italy
    Br J Pharmacol 160:1652-61. 2010
  10. pmc Drastic reduction of the slow gate of human muscle chloride channel (ClC-1) by mutation C277S
    A Accardi
    Istituto di Cibernetica e Biofisica, CNR, Via De Marini 6, I-16149 Genoa, Italy
    J Physiol 534:745-52. 2001

Collaborators

Detail Information

Publications46

  1. pmc Conformational changes in the pore of CLC-0
    Alessio Accardi
    Istituto di Biofisica, Sezione di Genova, CNR, I 16149 Genova, Italy
    J Gen Physiol 122:277-93. 2003
    ..These observations suggest that channel opening in CLC-0 consists in more than a movement of a side chain and that other parts of the channel and of the selectivity filter are probably involved...
  2. pmc Gating and flickery block differentially affected by rubidium in homomeric KCNQ1 and heteromeric KCNQ1/KCNE1 potassium channels
    M Pusch
    Istituto di Cibernetica e Biofisica, Consiglio Nazionale della Ricerche, Via De Marini 6, I 16149 Genova, Italy
    Biophys J 78:211-26. 2000
    ..The effects of KCNE1 on the conduction properties are consistent with an interaction of KCNE1 in the outer vestibule of the channel...
  3. ncbi Myotonia caused by mutations in the muscle chloride channel gene CLCN1
    Michael Pusch
    Istituto di Cibernetica e Biofisica, CNR, Genova, Italy
    Hum Mutat 19:423-34. 2002
    ..The large body of knowledge obtained for CLC-1 may also help to better understand the other CLC channels, three of which are also involved in genetic diseases...
  4. pmc Mechanism of block of single protopores of the Torpedo chloride channel ClC-0 by 2-(p-chlorophenoxy)butyric acid (CPB)
    M Pusch
    Istituto di Cibernetica e Biofisica, Consiglio Nazionale delle Ricerche, I 6149 Genova, Italy
    J Gen Physiol 118:45-62. 2001
    ..CPB block may become a useful tool to study the pore of ClC channels. As a first application, our results provide additional evidence for a double-barreled structure of ClC-0 and ClC-1...
  5. pmc Two open states and rate-limiting gating steps revealed by intracellular Na+ block of human KCNQ1 and KCNQ1/KCNE1 K+ channels
    M Pusch
    Istituto di Cibernetica e Biofisica, CNR, Via De Marini 6, I 16149 Genova, Italy
    J Physiol 533:135-43. 2001
    ..The rate-limiting step of homomeric KCNQ1 gating at positive voltages is the transition between these two open states. The rate-limiting step of the gating of KCNQ1/KCNE1 channels appears to be the entry into the first open state...
  6. ncbi Pharmacological characterization of chloride channels belonging to the ClC family by the use of chiral clofibric acid derivatives
    M Pusch
    Istituto di Cibernetica e Biofisica, CNR, Genova, Universita di Bari, Bari, Italy
    Mol Pharmacol 58:498-507. 2000
    ..No effects were observed on ClC-5 that shows less than 30% homology with ClC-1. Thus, CPP-like compounds may be useful both to gain insight into biophysical properties of ClC-1 and for searching tissue-specific therapeutic agents...
  7. pmc Chloride dependence of hyperpolarization-activated chloride channel gates
    M Pusch
    Centre for Molecular Neurobiology ZMNH, University of Hamburg, Hamburg, Germany
    J Physiol 515:341-53. 1999
    ..In contrast to the depolarization-activated fast gates of ClC-0 and ClC-1, the absence of Cl- favours channel opening. Lysine 556 may be important for the relevant binding site...
  8. ncbi Increase of the single-channel conductance of KvLQT1 potassium channels induced by the association with minK
    M Pusch
    Istituto di Cibernetica e Biofisica, CNR, Via De Marini 6, I 16149 Genova, Italy
    Pflugers Arch 437:172-4. 1998
    ..The larger conductance of heteromers explains in part their larger macroscopic conductance in heterologous expression systems. The molecular mechanism underlying the conductance increase remains to be identified...
  9. pmc Identification of sites responsible for the potentiating effect of niflumic acid on ClC-Ka kidney chloride channels
    G Zifarelli
    Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Genova, Italy
    Br J Pharmacol 160:1652-61. 2010
    ..We attempted to identify the amino acids involved in the activation of ClC-Ka by NFA...
  10. pmc Drastic reduction of the slow gate of human muscle chloride channel (ClC-1) by mutation C277S
    A Accardi
    Istituto di Cibernetica e Biofisica, CNR, Via De Marini 6, I-16149 Genoa, Italy
    J Physiol 534:745-52. 2001
    ..5. We conclude that the slow and fast gating processes of ClC-1, respectively, reflect the slow common pore gate and the single protopore gate of the double-barrelled ClC-1 channel...
  11. pmc Niflumic acid inhibits chloride conductance of rat skeletal muscle by directly inhibiting the CLC-1 channel and by increasing intracellular calcium
    A Liantonio
    Unità di Farmacologia, Dipartimento Farmacobiologico, Facolta di Farmacia, Universita di Bari, Bari, Italy
    Br J Pharmacol 150:235-47. 2007
    ..Here, we focused our attention on niflumic acid (NFA), a molecule belonging to the fenamates group of non-steroidal anti-inflammatory drugs (NSAID)...
  12. pmc Use dependence of tetrodotoxin block of sodium channels: a revival of the trapped-ion mechanism
    F Conti
    Istituto di Cibernetica e Biofisica, CNR, Genoa, Italy
    Biophys J 71:1295-312. 1996
    ..Reports arguing against the trapped-ion mechanism are critically discussed...
  13. ncbi CLC chloride channels and transporters: a biophysical and physiological perspective
    G Zifarelli
    CNR, Istituto di Biofisica, Via De Marini 6, 16149 Genova, Italy
    Rev Physiol Biochem Pharmacol 158:23-76. 2007
    ..The physiological significance of the Cl-/H+ antiport activity remains to be established...
  14. ncbi Single-channel analysis of a ClC-2-like chloride conductance in cultured rat cortical astrocytes
    M Nobile
    Institute of Cybernetics and Biophysics, CNR, Genoa, Italy
    FEBS Lett 479:10-4. 2000
    ..These results suggest that the astrocytic ClC-2-like Cl- current Iclh is mediated by a small-conductance Cl channel, which has the same structural motif as the Cl- channel prototype CIC-0...
  15. ncbi Channel or transporter? The CLC saga continues
    M Pusch
    Istituto di Biofisica, CNR, Via De Marini 6, I 16149 Genova, Italy
    Exp Physiol 91:149-52. 2006
    ..Apart from being useful biophysical tools, such drugs may provide a way to modulate protein function in vivo. With these tasks to be accomplished, it is definitely an exciting time in the chloride transport field...
  16. pmc Multimeric structure of ClC-1 chloride channel revealed by mutations in dominant myotonia congenita (Thomsen)
    K Steinmeyer
    Centre for Molecular Neurobiology ZMNH, Hamburg University, Germany
    EMBO J 13:737-43. 1994
    ..Analysis of both mutants shows independently that ClC-1 functions as a homooligomer with most likely four subunits...
  17. ncbi A chloride channel widely expressed in epithelial and non-epithelial cells
    A Thiemann
    Centre for Molecular Neurobiology ZMNH, Hamburg University, Hamburg, Germany
    Nature 356:57-60. 1992
    ..The presence of ClC-2 in such different cell types contrasts with the highly specialized expression of ClC-1 (ref. 9) and also with the cloned cation channels, and suggests that its function is important for most cells...
  18. doi CLC transport proteins in plants
    G Zifarelli
    Istituto di Biofisica, CNR, Via De Marini 6, I 16149 Genova, Italy
    FEBS Lett 584:2122-7. 2010
    ..Despite the different NO(3)(-) over Cl(-) selectivity of AtClC-a compared to the other CLC antiporters, it has similar transport properties. Other CLC homologues have been cloned in Arabidopsis, tobacco, rice and soybean...
  19. ncbi Unique structure and function of chloride transporting CLC proteins
    Michael Pusch
    Institute of Biophysics, Italian Research Council, Genoa I 16149, Italy
    IEEE Trans Nanobioscience 4:49-57. 2005
    ..These recent breakthroughs will allow us to study in further detail the structure, function, and the physiological and pathophysiological role of CLC proteins...
  20. ncbi Chloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5
    Alessandra Picollo
    Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Via De Marini 6, I 16149 Genova, Italy
    Nature 436:420-3. 2005
    ..For ClC-5, we estimated that Cl- and H+ transport contribute about equally to the total charge movement, raising the possibility that the coupled Cl-/H+ transport of ClC-4 and ClC-5 is of significant magnitude in vivo...
  21. pmc Proton sensing of CLC-0 mutant E166D
    Sonia Traverso
    Istituto di Biofisica, Consiglio Nazionale della Ricerche, Genova, Italy
    J Gen Physiol 127:51-65. 2006
    ..Voltage-independent protonation of D166 from the outside favors a low conductance state, whereas protonation from the inside favors the high conductance state...
  22. ncbi Molecular determinants of KCNQ (Kv7) K+ channel sensitivity to the anticonvulsant retigabine
    Anne Schenzer
    Institute of Biochemistry, Christian Albrechts University Kiel, D 24098 Kiel, Germany
    J Neurosci 25:5051-60. 2005
    ..Transfer of the tryptophan into the KCNQ1 scaffold resulted in retigabine-sensitive heteromers, suggesting that the tryptophan is necessary in all KCNQ subunits forming a functional tetramer to confer drug sensitivity...
  23. pmc Myotonia-related mutations in the distal C-terminus of ClC-1 and ClC-0 chloride channels affect the structure of a poly-proline helix
    Maria J Macias
    Institut de Recerca Biomèdica, Parc Cientific de Barcelona, Josep Samitier 1 5, Barcelona, E 08028, Spain
    Biochem J 403:79-87. 2007
    ..We provide the first experimental investigation of structural changes resulting from myotonia-causing mutations...
  24. ncbi Strong modulation by RFamide neuropeptides of the ASIC1b/3 heteromer in competition with extracellular calcium
    Xuanmao Chen
    University of Tubingen, Department of Physiology II, Gmelinstr 5, 72076 Tubingen, Germany University of Würzburg, Department of Physiology II, Röntgenring 9, 97070 Wurzburg, Germany
    Neuropharmacology 50:964-74. 2006
    ..Our results suggest that the ASIC1b/3 heteromer is a possible target for RFamide neuropeptides in the peripheral nervous system...
  25. pmc Molecular switch for CLC-K Cl- channel block/activation: optimal pharmacophoric requirements towards high-affinity ligands
    Antonella Liantonio
    Unità di Farmacologia and Dipartimento Farmacochimico, Dipartimento Farmacobiologico, Facolta di Farmacia, Universita di Bari, Bari 70125, Italy
    Proc Natl Acad Sci U S A 105:1369-73. 2008
    ..Based on our data, we established a pharmacophore model that will be useful for the development of drugs targeting CLC-K channels...
  26. pmc The muscle chloride channel ClC-1 is not directly regulated by intracellular ATP
    Giovanni Zifarelli
    Institute of Biophysics, National Research Council, Genova, Italy
    J Gen Physiol 131:109-16. 2008
    ..3) as well as at slightly acidic pH (pH 6.2). These results have implications for a general understanding of nucleotide regulation of CLC proteins and for the physiological role of ClC-1 in muscle excitation...
  27. pmc Intracellular proton regulation of ClC-0
    Giovanni Zifarelli
    Istituto di Biofisica, Consiglio Nazionale delle Ricerche, I 16149 Genova, Italy
    J Gen Physiol 132:185-98. 2008
    ..The gating model is in natural agreement with the finding that only the closing rate constant, but not the opening rate constant, depends on pH(int) and [Cl(-)](int)...
  28. pmc Identification of the Ca2+ blocking site of acid-sensing ion channel (ASIC) 1: implications for channel gating
    Martin Paukert
    Department of Physiology II, Gmelinstr 5, D 72076 Tubingen, Germany
    J Gen Physiol 124:383-94. 2004
    ..These results show that channel block by Ca2+ and H+ gating are not intrinsically linked...
  29. pmc Tight coupling of rubidium conductance and inactivation in human KCNQ1 potassium channels
    Guiscard Seebohm
    Department of Physiology, University of Utah, Salt Lake City, UT USA, Physiologisches Institut I, Tubingen, Germany
    J Physiol 552:369-78. 2003
    ....
  30. pmc Structural requisites of 2-(p-chlorophenoxy)propionic acid analogues for activity on native rat skeletal muscle chloride conductance and on heterologously expressed CLC-1
    Antonella Liantonio
    Unità di Farmacologia, Dipartimento Farmacobiologico, Facolta di Farmacia, Universita di Bari, Italy
    Br J Pharmacol 139:1255-64. 2003
    ....
  31. ncbi Pharmacological activation of normal and arrhythmia-associated mutant KCNQ1 potassium channels
    Guiscard Seebohm
    Department of Physiology and Eccles Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah 84112, USA
    Circ Res 93:941-7. 2003
    ..Most KCNQ1 mutant channels responded to R-L3 similarly to wild-type channels, but one mutant channel (G306R) was insensitive to R-L3 possibly because it disrupted a key component of the drug-binding site...
  32. ncbi Molecular modeling of p-chlorophenoxyacetic acid binding to the CLC-0 channel
    Oscar Moran
    Istituto di Biofisica, Sezione di Genova, CNR, Via De Marini, 6, I 16149 Genova, Italy
    Biochemistry 42:5176-85. 2003
    ....
  33. pmc Functional and structural conservation of CBS domains from CLC chloride channels
    Raúl Estévez
    Zentrum für Molekulare Neurobiologie Hamburg ZMNH, Hamburg University, Falkenried 94, D 20246 Hamburg, Germany
    J Physiol 557:363-78. 2004
    ..Thus, we propose that the structure of CBS domains from CLC channels is highly conserved and that they play a functional role in the common gate...
  34. ncbi Conservation of chloride channel structure revealed by an inhibitor binding site in ClC-1
    Raúl Estévez
    Zentrum fur Molekulare Neurobiologie Hamburg, ZMNH, Universitat Hamburg, Falkenried 94, D 20246 Hamburg, Germany
    Neuron 38:47-59. 2003
    ..Mutations in presumably Cl--coordinating residues yield additional insights into the structure and function of ClC-1. Our work shows that the structure of bacterial CLCs can be extrapolated with fidelity to mammalian Cl- channels...
  35. ncbi Structural insights into chloride and proton-mediated gating of CLC chloride channels
    Michael Pusch
    Istituto di Biofisica, CNR, Via De Marini, 6, I 16149 Genova, Italy
    Biochemistry 43:1135-44. 2004
    ..These studies confirm that the overall structure seems to be conserved from bacteria to humans. A full understanding of the mechanisms of gating of eukaryotic CLC channels is, however, still lacking...
  36. ncbi Mechanisms of block of muscle type CLC chloride channels (Review)
    Michael Pusch
    Istituto di Biofisica, CNR, Via De Marini 6, I 16149 Genova, Italy
    Mol Membr Biol 19:285-92. 2002
    ..They might also turn out to be useful to obtain information about the intricate coupling of gating and permeation that characterizes CLC channels...
  37. pmc Molecular determinants of differential pore blocking of kidney CLC-K chloride channels
    Alessandra Picollo
    Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Via De Marini 6, 16149 Genova, Italy
    EMBO Rep 5:584-9. 2004
    ..Both residues expose their side chains in the extracellular pore mouth, delineating the probable drug binding site. These novel CLC-K channel blockers are promising lead compounds for the development of new diuretic drugs...
  38. ncbi Molecular requisites for drug binding to muscle CLC-1 and renal CLC-K channel revealed by the use of phenoxy-alkyl derivatives of 2-(p-chlorophenoxy)propionic acid
    Antonella Liantonio
    Istituto di Cibernetica e Biofisica, Consiglio Nazionale delle Ricerche, Genova, Italy
    Mol Pharmacol 62:265-71. 2002
    ....
  39. pmc Gating competence of constitutively open CLC-0 mutants revealed by the interaction with a small organic Inhibitor
    Sonia Traverso
    Istituto di Biofisica, Sezione di Genova, CNR, Via De Marini, 6, I 16149 Genova, Italy
    J Gen Physiol 122:295-306. 2003
    ..Thus, if gating consists only in movement of this side-chain the mutant E166A should not be able to assume a closed conformation. It may thus be that fast gating in CLC-0 is more complex than anticipated from the bacterial structures...
  40. ncbi Mechanism of interaction of niflumic acid with heterologously expressed kidney CLC-K chloride channels
    Alessandra Picollo
    Istituto di Biofisica, CNR, Via De Marini, 6, I 16149 Genoa, Italy
    J Membr Biol 216:73-82. 2007
    ..The model predicts that ClC-Ka possesses two NFA binding sites: when only one site is occupied, NFA increases ClC-Ka currents, whereas the occupation of both binding sites leads to channel block...
  41. ncbi A two-holed story: structural secrets about ClC proteins become unraveled?
    Elena Babini
    Istituto di Biofisica, Consiglio Nazionale delle Ricerche, I 16149 Genova, Italy
    Physiology (Bethesda) 19:293-9. 2004
    ..In this short review, we will focus on recent results obtained on the X-ray structure and functional properties of the prokaryotic ClC-ec1 protein and some results obtained on the role of the cytoplasmic COOH terminus of mammalian ClCs...
  42. ncbi Investigations of pharmacologic properties of the renal CLC-K1 chloride channel co-expressed with barttin by the use of 2-(p-Chlorophenoxy)propionic acid derivatives and other structurally unrelated chloride channels blockers
    Antonella Liantonio
    Unità di Farmacologia, Dipartimento Farmacobiologico, Facolta di Farmacia, Universita di Bari, Bari, Italy
    J Am Soc Nephrol 15:13-20. 2004
    ..The newly identified substances provide a useful tool to investigate the biophysical and physiologic role of these renal channels and a starting point for the development of therapeutic drugs with diuretic action...
  43. ncbi Activation and inhibition of kidney CLC-K chloride channels by fenamates
    Antonella Liantonio
    Unità di Farmacologia, Dipartimento Farmacobiologico, Facolta di Farmacia, Universita di Bari, Bari, Italy
    Mol Pharmacol 69:165-73. 2006
    ..These molecules provide a starting point for identification of diuretics or drugs useful in the treatment of Bartter's syndrome...
  44. pmc Ca(2+)-activated chloride channels go molecular
    Michael Pusch
    Instituto di Biofisica, Genova, Italy
    J Gen Physiol 123:323-5. 2004
  45. ncbi Localization and functional analyses of the MLC1 protein involved in megalencephalic leukoencephalopathy with subcortical cysts
    Oscar Teijido
    Department of Biochemistry and Molecular Biology, Josep Samitier 1 5 Barcelona E 08028, Spain
    Hum Mol Genet 13:2581-94. 2004
    ..In summary, this study provides an explanation as to why mutations in MLC1 provoke the disease and points to a possible therapy for some patients...
  46. ncbi Determinants of anion-proton coupling in mammalian endosomal CLC proteins
    Anselm A Zdebik
    Leibniz Institut für Molekulare Pharmakologie FMP and Max Delbrück Centrum für Molekulare Medizin MDC, D 13125 Berlin, Germany
    J Biol Chem 283:4219-27. 2008
    ....