Structure and function of the CFTR chloride channel.

Structure and Function of the CFTR Chloride Channel. Physiol. Rev. 79, Suppl.: S23-S45, 1999. - The cystic fibrosis transmembrane conductance regulator (CFTR) is a unique member of the ABC transporter family that forms a novel Cl- channel. It is located predominantly in the apical membrane of epithelia where it mediates transepithelial salt and liquid movement. Dysfunction of CFTR causes the genetic disease cystic fibrosis. The CFTR is composed of five domains: two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBDs), and a regulatory (R) domain. Here we review the structure and function of this unique channel, with a focus on how the various domains contribute to channel function. The MSDs form the channel pore, phosphorylation of the R domain determines channel activity, and ATP hydrolysis by the NBDs controls channel gating. Current knowledge of CFTR structure and function may help us understand better its mechanism of action, its role in electrolyte transport, its dysfunction in cystic fibrosis, and its relationship to other ABC transporters.

[1]  W. Guggino,et al.  The Second Half of the Cystic Fibrosis Transmembrane Conductance Regulator Forms a Functional Chloride Channel* , 1998, The Journal of Biological Chemistry.

[2]  D. Sheppard,et al.  Comparison of the gating behaviour of human and murine cystic fibrosis transmembrane conductance regulator Cl− channels expressed in mammalian cells , 1998, The Journal of physiology.

[3]  S. S. Smith,et al.  Cystic fibrosis transmembrane conductance regulator (CFTR) anion binding as a probe of the pore. , 1998, Biophysical journal.

[4]  A. Takahashi,et al.  FLAG epitope positioned in an external loop preserves normal biophysical properties of CFTR. , 1997, American journal of physiology. Cell physiology.

[5]  P. Davis,et al.  Function of the R Domain in the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel* , 1997, The Journal of Biological Chemistry.

[6]  Joseph F. Cotten,et al.  Covalent Modification of the Regulatory Domain Irreversibly Stimulates Cystic Fibrosis Transmembrane Conductance Regulator* , 1997, The Journal of Biological Chemistry.

[7]  M. Welsh,et al.  Block by MOPS reveals a conformation change in the CFTR pore produced by ATP hydrolysis. , 1997, The American journal of physiology.

[8]  P. Linsdell,et al.  Multi-Ion Mechanism for Ion Permeation and Block in the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel , 1997, The Journal of general physiology.

[9]  L. Tsui,et al.  Permeability of Wild-Type and Mutant Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channels to Polyatomic Anions , 1997, The Journal of general physiology.

[10]  P. Linsdell,et al.  Halide Permeation in Wild-Type and Mutant Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channels , 1997, The Journal of general physiology.

[11]  H. A. Berger,et al.  Protein phosphatase 2C dephosphorylates and inactivates cystic fibrosis transmembrane conductance regulator. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[12]  J. Riordan,et al.  Disease-associated mutations in cytoplasmic loops 1 and 2 of cystic fibrosis transmembrane conductance regulator impede processing or opening of the channel. , 1997, Biochemistry.

[13]  M. Welsh,et al.  Stimulation of CFTR activity by its phosphorylated R domain , 1997, Nature.

[14]  D. Sheppard,et al.  Mechanism of Glibenclamide Inhibition of Cystic Fibrosis Transmembrane Conductance Regulator Cl− Channels Expressed in a Murine Cell Line , 1997, The Journal of physiology.

[15]  S. S. Smith,et al.  CFTR activation: additive effects of stimulatory and inhibitory phosphorylation sites in the R domain. , 1997, The American journal of physiology.

[16]  E. Auerswald,et al.  A recombinant polypeptide model of the second nucleotide‐binding fold of the cystic fibrosis transmembrane conductance regulator functions as an active ATPase, GTPase and adenylate kinase , 1997, FEBS letters.

[17]  J. Annereau,et al.  A novel model for the first nucleotide binding domain of the cystic fibrosis transmembrane conductance regulator , 1997, FEBS letters.

[18]  C. Higgins,et al.  Structure of the Multidrug Resistance P-glycoprotein to 2.5 nm Resolution Determined by Electron Microscopy and Image Analysis* , 1997, The Journal of Biological Chemistry.

[19]  J. Foskett,et al.  Cystic Fibrosis Transmembrane Conductance Regulator-associated ATP and Adenosine 3′-Phosphate 5′-Phosphosulfate Channels in Endoplasmic Reticulum and Plasma Membranes* , 1997, The Journal of Biological Chemistry.

[20]  M. Akabas,et al.  Locating the Anion-selectivity Filter of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Chloride Channel , 1997, The Journal of general physiology.

[21]  J. Hanrahan,et al.  Phosphorylation by Protein Kinase C Is Required For Acute Activation of Cystic Fibrosis Transmembrane Conductance Regulator by Protein Kinase A* , 1997, The Journal of Biological Chemistry.

[22]  M. Welsh,et al.  Association of domains within the cystic fibrosis transmembrane conductance regulator. , 1997, Biochemistry.

[23]  T. Machen,et al.  The tyrosine kinase p60c-src regulates the fast gate of the cystic fibrosis transmembrane conductance regulator chloride channel. , 1996, Biophysical journal.

[24]  M. Drumm,et al.  Human epithelial cystic fibrosis transmembrane conductance regulator without exon 5 maintains partial chloride channel function in intracellular membranes. , 1996, Biophysical journal.

[25]  J. Rommens,et al.  ATPase Activity of the Cystic Fibrosis Transmembrane Conductance Regulator* , 1996, The Journal of Biological Chemistry.

[26]  J. Riordan,et al.  Cytoplasmic Loop Three of Cystic Fibrosis Transmembrane Conductance Regulator Contributes to Regulation of Chloride Channel Activity* , 1996, The Journal of Biological Chemistry.

[27]  P. Linsdell,et al.  Disulphonic stilbene block of cystic fibrosis transmembrane conductance regulator Cl‐ channels expressed in a mammalian cell line and its regulation by a critical pore residue. , 1996, The Journal of physiology.

[28]  M. Welsh,et al.  Function of Xenopus Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Cl− Channels and Use of Human-Xenopus Chimeras to Investigate the Pore Properties of CFTR* , 1996, The Journal of Biological Chemistry.

[29]  A S Verkman,et al.  Identification of protein kinase A phosphorylation sites on NBD1 and R domains of CFTR using electrospray mass spectrometry with selective phosphate ion monitoring , 1996, Protein science : a publication of the Protein Society.

[30]  Joseph F. Cotten,et al.  Effect of Cystic Fibrosis-associated Mutations in the Fourth Intracellular Loop of Cystic Fibrosis Transmembrane Conductance Regulator* , 1996, The Journal of Biological Chemistry.

[31]  P. Linsdell,et al.  Flickery block of single CFTR chloride channels by intracellular anions and osmolytes. , 1996, The American journal of physiology.

[32]  A. K. Singh,et al.  Glibenclamide blockade of CFTR chloride channels. , 1996, The American journal of physiology.

[33]  P. Quinton,et al.  Hydrolytic and nonhydrolytic interactions in the ATP regulation of CFTR Cl- conductance. , 1996, The American journal of physiology.

[34]  B. Horowitz,et al.  Cystic fibrosis gene encodes a cAMP-dependent chloride channel in heart. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[35]  J. Riordan,et al.  Disease-associated Mutations in the Fourth Cytoplasmic Loop of Cystic Fibrosis Transmembrane Conductance Regulator Compromise Biosynthetic Processing and Chloride Channel Activity* , 1996, The Journal of Biological Chemistry.

[36]  M. Welsh,et al.  Contribution of Proline Residues in the Membrane-spanning Domains of Cystic Fibrosis Transmembrane Conductance Regulator to Chloride Channel Function* , 1996, The Journal of Biological Chemistry.

[37]  M. Akabas,et al.  Identification of cystic fibrosis transmembrane conductance regulator channel-lining residues in and flanking the M6 membrane-spanning segment. , 1996, Biophysical journal.

[38]  A. K. Singh,et al.  Tolbutamide causes open channel blockade of cystic fibrosis transmembrane conductance regulator Cl- channels. , 1996, Biophysical journal.

[39]  H. Dietz,et al.  Both the wild type and a functional isoform of CFTR are expressed in kidney. , 1996, The American journal of physiology.

[40]  C. Bear,et al.  Purified Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Does Not Function as an ATP Channel (*) , 1996, The Journal of Biological Chemistry.

[41]  R. Frizzell,et al.  Lack of Conventional ATPase Properties in CFTR Chloride Channel Gating , 1996, The Journal of Membrane Biology.

[42]  J. Hanrahan,et al.  CFTR Channels Expressed in CHO Cells Do Not Have Detectable ATP Conductance , 1996, The Journal of Membrane Biology.

[43]  K. Gunderson,et al.  Failure of the Cystic Fibrosis Transmembrane Conductance Regulator to Conduct ATP , 1996, Science.

[44]  M. Drumm,et al.  Phosphorylation-dependent Block of Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel by Exogenous R Domain Protein (*) , 1996, The Journal of Biological Chemistry.

[45]  M. Drumm,et al.  Slow conversions among subconductance states of cystic fibrosis transmembrane conductance regulator chloride channel. , 1996, Biophysical journal.

[46]  F. Collins,et al.  CFTR: the nucleotide binding folds regulate the accessibility and stability of the activated state , 1996, The Journal of general physiology.

[47]  M. Welsh,et al.  Structural and functional similarities between the nucleotide-binding domains of CFTR and GTP-binding proteins. , 1995, Biophysical journal.

[48]  M. Drumm,et al.  Intracellular Loop between Transmembrane Segments IV and V of Cystic Fibrosis Transmembrane Conductance Regulator Is Involved in Regulation of Chloride Channel Conductance State (*) , 1995, The Journal of Biological Chemistry.

[49]  J. Inazawa,et al.  Reconstitution of IKATP: An Inward Rectifier Subunit Plus the Sulfonylurea Receptor , 1995, Science.

[50]  P. Pedersen,et al.  The First Nucleotide Binding Fold of the Cystic Fibrosis Transmembrane Conductance Regulator Can Function as an Active ATPase (*) , 1995, The Journal of Biological Chemistry.

[51]  M. Welsh,et al.  Pyrophosphate Stimulates Wild-type and Mutant Cystic Fibrosis Transmembrane Conductance Regulator Cl− Channels (*) , 1995, The Journal of Biological Chemistry.

[52]  K. Gunderson,et al.  Conformational states of CFTR associated with channel gating: The role of ATP binding and hydrolysis , 1995, Cell.

[53]  G. Cutting,et al.  CFTR regulates outwardly rectifying chloride channels through an autocrine mechanism involving ATP , 1995, Cell.

[54]  P. Manavalan,et al.  Sequence homologies between nucleotide binding regions of CFTR and G‐proteins suggest structural and functional similarities , 1995, FEBS letters.

[55]  T. Flotte,et al.  Alternate Translation Initiation Codons Can Create Functional Forms of Cystic Fibrosis Transmembrane Conductance Regulator (*) , 1995, The Journal of Biological Chemistry.

[56]  T. Begenisich,et al.  Volume‐activated chloride channels in rat parotid acinar cells. , 1995, The Journal of physiology.

[57]  M. Drumm,et al.  Rectification of whole cell cystic fibrosis transmembrane conductance regulator chloride current. , 1995, The American journal of physiology.

[58]  R. Frizzell,et al.  Regulation of CFTR Cl- channel gating by ADP and ATP analogues , 1995, The Journal of general physiology.

[59]  J. Riordan,et al.  cAMP-dependent Protein Kinase-mediated Phosphorylation of Cystic Fibrosis Transmembrane Conductance Regulator Residue Ser-753 and Its Role in Channel Activation (*) , 1995, The Journal of Biological Chemistry.

[60]  M. Welsh,et al.  The Two Nucleotide-binding Domains of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Have Distinct Functions in Controlling Channel Activity (*) , 1995, The Journal of Biological Chemistry.

[61]  X. Chang,et al.  Mutation of potential phosphorylation sites in the recombinant R domain of the cystic fibrosis transmembrane conductance regulator has significant effects on domain conformation. , 1995, Biochemical and biophysical research communications.

[62]  A. Nairn,et al.  Regulation of CFTR channel gating. , 1994, Trends in biochemical sciences.

[63]  L. Tsui,et al.  Phosphatase inhibitors activate normal and defective CFTR chloride channels. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[64]  T. Machen,et al.  CFTR displays voltage dependence and two gating modes during stimulation , 1994, The Journal of general physiology.

[65]  Henry A. Lester,et al.  Novel pore-lining residues in CFTR that govern permeation and open-channel block , 1994, Neuron.

[66]  H. Cantiello,et al.  The cystic fibrosis transmembrane conductance regulator is a dual ATP and chloride channel. , 1994, The Journal of biological chemistry.

[67]  K. Gunderson,et al.  Effects of pyrophosphate and nucleotide analogs suggest a role for ATP hydrolysis in cystic fibrosis transmembrane regulator channel gating. , 1994, The Journal of biological chemistry.

[68]  T. Jensen,et al.  Mapping of cystic fibrosis transmembrane conductance regulator membrane topology by glycosylation site insertion. , 1994, The Journal of biological chemistry.

[69]  J. Stokes,et al.  Effect of cAMP on intracellular and extracellular ATP content of Cl- -secreting epithelia and 3T3 fibroblasts. , 1994, The Journal of biological chemistry.

[70]  R. Frizzell,et al.  ATP alters current fluctuations of cystic fibrosis transmembrane conductance regulator: evidence for a three-state activation mechanism , 1994, The Journal of general physiology.

[71]  M. Akabas,et al.  Amino acid residues lining the chloride channel of the cystic fibrosis transmembrane conductance regulator. , 1994, The Journal of biological chemistry.

[72]  G. Nagel,et al.  Regulation of the gating of cystic fibrosis transmembrane conductance regulator C1 channels by phosphorylation and ATP hydrolysis. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[73]  M. Welsh,et al.  Effect of ATP concentration on CFTR Cl- channels: a kinetic analysis of channel regulation. , 1994, Biophysical journal.

[74]  J. Riordan,et al.  A two‐domain model for the R domain of the cystic fibrosis transmembrane conductance regulator based on sequence similarities , 1994, FEBS letters.

[75]  J. Riordan,et al.  Phosphorylation by cAMP-dependent protein kinase causes a conformational change in the R domain of the cystic fibrosis transmembrane conductance regulator. , 1994, Biochemistry.

[76]  M. Welsh,et al.  The amino-terminal portion of CFTR forms a regulated CI− channel , 1994, Cell.

[77]  A. Nairn,et al.  Coupling of CFTR Cl− channel gating to an ATP hydrolysis cycle , 1994, Neuron.

[78]  M Montal,et al.  Identification of an ion channel-forming motif in the primary structure of CFTR, the cystic fibrosis chloride channel. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[79]  M. Welsh,et al.  Stoichiometry of recombinant cystic fibrosis transmembrane conductance regulator in epithelial cells and its functional reconstitution into cells in vitro. , 1994, The Journal of biological chemistry.

[80]  C. Panagiotidis,et al.  Tinkering with transporters: Periplasmic binding protein-dependent maltose transport inE. coli , 1993, Journal of bioenergetics and biomembranes.

[81]  A. Nairn,et al.  Cardiac Chloride Channels: Incremental Regulation by Phosphorylation/Dephosphorylation a , 1993 .

[82]  L. Tsui,et al.  Multi-ion pore behaviour in the CFTR chloride channel , 1993, Nature.

[83]  F. Collins,et al.  Functional roles of the nucleotide-binding folds in the activation of the cystic fibrosis transmembrane conductance regulator. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[84]  M. Akabas,et al.  Amino acids lining the channel of the gamma-aminobutyric acid type A receptor identified by cysteine substitution. , 1993, The Journal of biological chemistry.

[85]  H. A. Berger,et al.  Regulation of the cystic fibrosis transmembrane conductance regulator Cl- channel by negative charge in the R domain. , 1993, The Journal of biological chemistry.

[86]  M. Welsh,et al.  Cystic fibrosis transmembrane conductance regulator splice variants are not conserved and fail to produce chloride channels , 1993, Nature Genetics.

[87]  M. Welsh,et al.  Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis , 1993, Cell.

[88]  J. Riordan,et al.  Voltage-dependent block of the cystic fibrosis transmembrane conductance regulator Cl- channel by two closely related arylaminobenzoates , 1993, The Journal of general physiology.

[89]  M. Welsh,et al.  5'-Adenylylimidodiphosphate does not activate CFTR chloride channels in cell-free patches of membrane. , 1993, The American journal of physiology.

[90]  B. Horowitz,et al.  Alternative splicing of CFTR Cl- channels in heart. , 1993, The American journal of physiology.

[91]  J. Riordan,et al.  Protein kinase A (PKA) still activates CFTR chloride channel after mutagenesis of all 10 PKA consensus phosphorylation sites. , 1993, The Journal of biological chemistry.

[92]  M. Horie,et al.  Functionally distinct phospho-forms underlie incremental activation of protein kinase-regulated Cl- conductance in mammalian heart , 1993, The Journal of general physiology.

[93]  H. A. Berger,et al.  Identification of revertants for the cystic fibrosis ΔF508 mutation using STE6-CFTR chimeras in yeast , 1993, Cell.

[94]  M. Welsh,et al.  Mutations in CFTR associated with mild-disease-form CI- channels with altered pore properties , 1993, Nature.

[95]  M. Wilke,et al.  Low-conductance chloride channels in IEC-6 and CF nasal cells expressing CFTR. , 1993, American Journal of Physiology.

[96]  D. Clarke,et al.  Functional consequences of proline mutations in the predicted transmembrane domain of P-glycoprotein. , 1993, The Journal of biological chemistry.

[97]  H. A. Berger,et al.  Regulation of the cystic fibrosis transmembrane conductance regulator Cl- channel by specific protein kinases and protein phosphatases. , 1993, The Journal of biological chemistry.

[98]  M. Welsh,et al.  Partial purification of the cystic fibrosis transmembrane conductance regulator. , 1992, The Journal of biological chemistry.

[99]  A. Greenough,et al.  Lung function in 6–20 month old infants born very preterm but without respiratory troubles , 1992, Pediatric pulmonology.

[100]  A. Verkman,et al.  A multifunctional aqueous channel formed by CFTR. , 1992, Science.

[101]  P. Quinton,et al.  Control of CFTR chloride conductance by ATP levels through non-hydrolytic binding , 1992, Nature.

[102]  C. Higgins,et al.  ABC transporters: from microorganisms to man. , 1992, Annual review of cell biology.

[103]  M. Welsh,et al.  Effect of ATP-sensitive K+ channel regulators on cystic fibrosis transmembrane conductance regulator chloride currents , 1992, The Journal of general physiology.

[104]  M. Welsh,et al.  Regulation by ATP and ADP of CFTR chloride channels that contain mutant nucleotide-binding domains. , 1992, Science.

[105]  P. Greengard,et al.  Phosphorylation of the cystic fibrosis transmembrane conductance regulator. , 1992, The Journal of biological chemistry.

[106]  M. Welsh,et al.  Cyclic AMP-dependent protein kinase activation of cystic fibrosis transmembrane conductance regulator chloride channels in planar lipid bilayers. , 1992, The Journal of biological chemistry.

[107]  C. Higgins,et al.  Identification and developmental expression of the Xenopus laevis cystic fibrosis transmembrane conductance regulator gene. , 1992, Human molecular genetics.

[108]  E. Rojas,et al.  Intrinsic anion channel activity of the recombinant first nucleotide binding fold domain of the cystic fibrosis transmembrane regulator protein. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[109]  R. Frizzell,et al.  Anion permeation in an apical membrane chloride channel of a secretory epithelial cell , 1992, The Journal of general physiology.

[110]  J. Riordan,et al.  Purification and functional reconstitution of the cystic fibrosis transmembrane conductance regulator (CFTR) , 1992, Cell.

[111]  F. Collins,et al.  Chloride conductance expressed by delta F508 and other mutant CFTRs in Xenopus oocytes. , 1991, Science.

[112]  Matthew P. Anderson,et al.  Nucleoside triphosphates are required to open the CFTR chloride channel , 1991, Cell.

[113]  J. Riordan,et al.  Cl- channel activity in Xenopus oocytes expressing the cystic fibrosis gene. , 1991, The Journal of biological chemistry.

[114]  H. A. Berger,et al.  Identification and regulation of the cystic fibrosis transmembrane conductance regulator-generated chloride channel. , 1991, The Journal of clinical investigation.

[115]  M. Welsh,et al.  Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel , 1991, Cell.

[116]  E. Krebs,et al.  Consensus sequences as substrate specificity determinants for protein kinases and protein phosphatases. , 1991, The Journal of biological chemistry.

[117]  J. Riordan,et al.  Phosphorylation-regulated CI− channel in CHO cells stably expressing the cystic fibrosis gene , 1991, Nature.

[118]  M. Welsh,et al.  Maturation and function of cystic fibrosis transmembrane conductance regulator variants bearing mutations in putative nucleotide-binding domains 1 and 2 , 1991, Molecular and cellular biology.

[119]  M. Welsh,et al.  Calcium and cAMP activate different chloride channels in the apical membrane of normal and cystic fibrosis epithelia. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[120]  Matthew P. Anderson,et al.  Effect of deleting the R domain on CFTR-generated chloride channels. , 1991, Science.

[121]  M. Welsh,et al.  Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. , 1991, Science.

[122]  L. Tsui,et al.  Expression of the cystic fibrosis gene in non-epithelial invertebrate cells produces a regulated anion conductance , 1991, Cell.

[123]  M. Welsh,et al.  Generation of cAMP-activated chloride currents by expression of CFTR. , 1991, Science.

[124]  R. Aldrich,et al.  Restoration of inactivation in mutants of Shaker potassium channels by a peptide derived from ShB , 1990, Science.

[125]  T Hoshi,et al.  Biophysical and molecular mechanisms of Shaker potassium channel inactivation , 1990, Science.

[126]  J. Hanrahan,et al.  Low‐conductance chloride channel activated by cAMP in the epithelial cell line T84 , 1990, FEBS letters.

[127]  G. Ames,et al.  Bacterial periplasmic permeases belong to a family of transport proteins operating from to human: Traffic ATPases , 1990 .

[128]  G. Ames,et al.  Bacterial periplasmic permeases belong to a family of transport proteins operating from Escherichia coli to human: Traffic ATPases. , 1990, FEMS microbiology reviews.

[129]  Michael J. Hartshorn,et al.  Structural model of ATP-binding proteing associated with cystic fibrosis, multidrug resistance and bacterial transport , 1990, Nature.

[130]  L. Tsui,et al.  Erratum: Identification of the Cystic Fibrosis Gene: Cloning and Characterization of Complementary DNA , 1989, Science.

[131]  B. Sakmann,et al.  Mechanism of anion permeation through channels gated by glycine and gamma‐aminobutyric acid in mouse cultured spinal neurones. , 1987, The Journal of physiology.

[132]  L. Cantley,et al.  Na+ transport in cystic fibrosis respiratory epithelia. Abnormal basal rate and response to adenylate cyclase activation. , 1986, The Journal of clinical investigation.

[133]  C. Deber,et al.  Hypothesis about the function of membrane-buried proline residues in transport proteins. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[134]  C. Hales,et al.  THE SULPHONYLUREA RECEPTOR MAY BE AN ATP-SENSITIVE POTASSIUM CHANNEL , 1985, The Lancet.

[135]  B. Hille,et al.  Lyotropic anions. Na channel gating and Ca electrode response , 1983, The Journal of general physiology.

[136]  Junxia Xie,et al.  Phosphorylation-dependent Block of Cystic Fibrosis , 1996 .

[137]  I. Pastan,et al.  Multidrug Resistance Transporter , 1996 .

[138]  M. Chen,et al.  Membrane insertion, processing, and topology of cystic fibrosis transmembrane conductance regulator (CFTR) in microsomal membranes. , 1996, Molecular membrane biology.

[139]  M. Welsh,et al.  Mutation of R555 in CFTR-delta F508 enhances function and partially corrects defective processing. , 1996, Receptors & channels.

[140]  G. Nagel,et al.  The CFTR chloride channel of mammalian heart. , 1995, Annual review of physiology.

[141]  T. Tameyasu.  Velocity and extent of electrically-triggered and spontaneous contractions in rat ventricular myocyte: relation to cell size and sarcomere length. , 1994, The Japanese journal of physiology.

[142]  G. Pollack,et al.  Force-length relation of isometric sarcomeres in fixed-end tetani. , 1993, The American journal of physiology.

[143]  C. Bowers,et al.  Maintenance of contractility in dissociated smooth muscle: low-density cultures in a defined medium. , 1993, The American journal of physiology.

[144]  M. Welsh,et al.  Effect of deletion mutations on the function of CFTR chloride channels. , 1993, Receptors & channels.

[145]  M. Welsh,et al.  Localization of cystic fibrosis transmembrane conductance regulator in chloride secretory epithelia. , 1992, The Journal of clinical investigation.

[146]  F. Ashcroft,et al.  Properties and functions of ATP-sensitive K-channels. , 1990, Cellular signalling.

[147]  J. Richardson,et al.  Principles and Patterns of Protein Conformation , 1989 .

[148]  A. Gilman,et al.  G proteins: transducers of receptor-generated signals. , 1987, Annual review of biochemistry.

[149]  B. Hille.  Na Channel Gating and Ca Electrode Response , 1983 .

[150]  E. Wright,et al.  Anion selectivity in biological systems. , 1977, Physiological reviews.