Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Ion channels versus ion pumps: the principal difference, in principle

Nature Reviews Molecular Cell Biology volume 10, pages 344–352 (2009)Cite this article

Key Points

  • Ions move across cell membranes through either ion channels or ion pumps. Ions flow passively through ion channels, down electrical and concentration gradients, at speeds that can approach the diffusion limit. By contrast, ion pumps generate those gradients by expending energy (usually in the form of ATP, or gradients of sodium ions or protons) to slowly move ions thermodynamically uphill.

  • So that ions flow only when needed, the pathway through an ion channel can be opened and closed by conformational changes that displace an obstruction called a gate. Although a channel needs only a single gate, a pump needs at least two gates that must open and close strictly alternately to provide access to its binding sites from only one side of the membrane at a time. A pump's two gates should never both be open, lest it behave like an ion channel and allow dissipative ion flow that would in an instant undo the pump's concentrative work.

  • X-ray crystal structures of cation channels and cation pumps perfected by evolution reveal distinct design principles. In ion channels, the narrow region that recognizes and selects ions for conduction is physically separated from the activation gate. But in pumps, these functions are intertwined, as the ion-binding pocket is remodelled with each alternation of access. The need for two gating reactions per transport event accounts for the orders of magnitude slower ion movement through pumps than through channels.

  • High-resolution structures have also been obtained of a member of a family that contains both anion channels and anion pumps. The structures are of a pump, but structural and functional analysis of mutants suggests that only microscopic differences distinguish the two family branches from one another. Moreover, channel members bear vestiges of pump behaviour, implying that the channels evolved from a pump member in which one of the gates failed.

  • There are other examples of ion channels that belong to pump families, and that likely arose from inherited gate dysfunction. Pharmacological interference with gate function can also transform a pump into an ion channel. There are even hybrid molecules that, while pumping their substrate, allow uncoupled, channel-like, electrodiffusive ion leakage.

  • Ion transport proteins can thus span a wide spectrum, from highly evolved ion channels to evolutionarily perfected ion pumps. Somewhere between these extremes, the distinction between channels and pumps becomes blurred. Determining the structures and mechanisms of ion transport proteins throughout the spectrum remains an important challenge.

Abstract

The incessant traffic of ions across cell membranes is controlled by two kinds of border guards: ion channels and ion pumps. Open channels let selected ions diffuse rapidly down electrical and concentration gradients, whereas ion pumps labour tirelessly to maintain the gradients by consuming energy to slowly move ions thermodynamically uphill. Because of the diametrically opposed tasks and the divergent speeds of channels and pumps, they have traditionally been viewed as completely different entities, as alike as chalk and cheese. But new structural and mechanistic information about both of these classes of molecular machines challenges this comfortable separation and forces its re-evaluation.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Ion channels versus ion pumps, in principle.
Figure 2: Crystal structures of a real channel and a real pump reveal clear differences.
Figure 3: A Cl ion channel evolved from a Cl/H exchanger.
Figure 4: A Cl ion channel evolved from an ABC transporter.

Similar content being viewed by others

References

  1. Hille, B. Ion Channels of Excitable Membranes (Sinauer, Sunderland, 2001).

    Google Scholar 

  2. Sakmann, B. & Neher, E. Single-Channel Recording (Plenum, New York, 1995).

    Google Scholar 

  3. Läuger, P. A channel mechanism for electrogenic ion pumps. Biochim. Biophys. Acta 552, 143–161 (1979).

    PubMed  Google Scholar 

  4. Patlak, C. S. Contributions to the theory of active transport. II. The gate-type non-carrier mechanism and generalization concerning tracer glow efficiency, and measurement of energy expenditure. Bull. Math. Biophys. 19, 209–235 (1957).

    Google Scholar 

  5. Vidaver, G. A. Inhibition of parallel flux and augmentation of counter flux shown by transport models not involving a mobile carrier. J. Theor. Biol. 10, 301–306 (1966).

    CAS  PubMed  Google Scholar 

  6. Jardetzky, O. Simple allosteric model for membrane pumps. Nature 27, 969–970 (1966).

    Google Scholar 

  7. MacKinnon, R. Potassium channels. FEBS Lett. 555, 62–65 (2003).

    CAS  PubMed  Google Scholar 

  8. Zhou, Y., Morais-Cabral, J. H., Kaufman, A. & MacKinnon, R. Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 Å resolution. Nature 414, 43–48 (2001). This high-resolution structure revealed the mechanism of the K ion channel selectivity filter. Each of its four K ion sites lies at the centre of a cage of eight carbonyl oxygens that mimic those of the eight water molecules found surrounding the hydrated K ion in the large central cavity. The selectivity filter minimizes the energetic cost of transferring K ions from the aqueous environment to the K ion channel interior.

    CAS  PubMed  Google Scholar 

  9. Morais-Cabral, J. H., Zhou, Y. & MacKinnon, R. Energetic optimization of ion conduction rate by the K+ selectivity filter. Nature 414, 37–42 (2001).

    CAS  PubMed  Google Scholar 

  10. Post, R. L., Hegyvary, C. & Kume, S. Activation by adenosine triphosphate in the phosphorylation kinetics of sodium and potassium ion transport adenosine triphosphatase. J. Biol. Chem. 247, 6530–6540 (1972).

    CAS  PubMed  Google Scholar 

  11. Toyoshima, C., Nakasako, M., Nomura, H. & Ogawa, H. Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 Å resolution. Nature 405, 647–655 (2000). The first X-ray crystal structure of a P-type ATPase ion pump. The two transported Ca ions were found buried side by side in their binding sites, deep within the transmembrane domain and inaccessible from either side.

    CAS  PubMed  Google Scholar 

  12. Toyoshima, C., Nomura, H. & Tsuda, T. Lumenal gating mechanism revealed in calcium pump crystal structures with phosphate analogues. Nature 432, 361–368 (2004).

    CAS  PubMed  Google Scholar 

  13. Toyoshima, C., Norimatsu, Y., Iwasawa, S., Tsuda, T. & Ogawa, H. How processing of aspartylphosphate is coupled to lumenal gating of the ion pathway in the calcium pump. Proc. Natl Acad. Sci. USA 104, 19831–19836 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Toyoshima, C. & Nomura, H. Structural changes in the calcium pump accompanying the dissociation of calcium. Nature 418, 605–611 (2002).

    CAS  PubMed  Google Scholar 

  15. Toyoshima, C. & Mizutani, T. Crystal structure of the calcium pump with a bound ATP analogue. Nature 430, 529–535 (2004).

    CAS  PubMed  Google Scholar 

  16. Møller, J. V., Nissen, P., Sorensen, T. L.-M. & le Marie, M. Transport mechanism of the sarcoplasmic reticulum Ca2+-ATPase pump. Curr. Opin. Struct. Biol. 15, 387–393 (2005).

    PubMed  Google Scholar 

  17. Olesen, C., Sorensen, T. L., Nielsen, R. C., Møller, J. V. & Nissen, P. Dephosphorylation of the calcium pump coupled to counterion occlusion. Science 306, 2251–2255 (2004).

    CAS  PubMed  Google Scholar 

  18. Olesen, C. et al. The structural basis of calcium transport by the calcium pump. Nature 450, 1036–1042 (2007).

    CAS  PubMed  Google Scholar 

  19. Sørensen, T. L. M., Møller, J. V. & Nissen, P. Phosphoryl transfer and calcium ion occlusion in the calcium pump. Science 304, 1672–1675 (2004).

    PubMed  Google Scholar 

  20. Morth, J. P. et al. Crystal structure of the sodium-potassium pump. Nature 450, 1043–1049 (2007).

    CAS  PubMed  Google Scholar 

  21. Accardi, A. & Miller, C. Secondary active transport mediated by a prokaryotic homologue of ClC Cl− channels. Nature 427, 803–807 (2004). Using electrophysiological and biochemical functional assays on the same preparation of prokaryotic ClC proteins (ClC-ec1) that had been used for X-ray crystallography, this study came to the shocking conclusion that ClC-ec1 is a Cl/H exchange pump, rather than the Cl ion channel initially assumed.

    CAS  PubMed  Google Scholar 

  22. Miller, C. Open-state substructure of single chloride channels from Torpedo electroplax. Philos. Trans. R. Soc. Lond. B Biol. Sci. 299, 401–411 (1982).

    CAS  PubMed  Google Scholar 

  23. Middleton, R. E., Pheasant, D. J. & Miller, C. Homodimeric architecture of a CIC-type chloride ion channel. Nature 383, 337–340 (1996).

    CAS  PubMed  Google Scholar 

  24. Ludewig, U., Pusch, M. & Jentsch, T. J. Two physcially distinct pores in the demeric CIC-0 chloride channel. Nature 383, 340–343 (1996).

    CAS  PubMed  Google Scholar 

  25. Dutzler, R., Campbell, E. B., Cadene, M., Chait, B. T. & MacKinnon, R. X-ray structure of a ClC chloride channel at 3.0 Å reveals the molecular basis of anion selectivity. Nature 415, 287–294 (2002).

    CAS  PubMed  Google Scholar 

  26. Jentsch, T. J., Poët, M., Fuhrmann, J. C. & Zdebik, A. A. Physiological functions of CLC Cl− channels gleaned from human genetic disease and mouse models. Annu. Rev. Physiol. 67, 779–807 (2005).

    CAS  PubMed  Google Scholar 

  27. Dutzler, R., Campbell, E. B. & MacKinnon, R. Gating the selectivity filter in ClC chloride channels. Science 300, 108–112 (2003). In this structural study, a Glu residue side chain that occupies an anion site in the ion pathway of ClC-ec1 was found to swing away on protonation, unblocking the pathway and allowing a Cl ion to take its place. The residue was identified as a fast gate because mutation of the analogous Glu residue in ClC-0 channels to Gln almost abolished fast gating, leaving the channels mostly open.

    CAS  PubMed  Google Scholar 

  28. Chen, M. F. & Chen, T. Y. Different fast-gate regulation by external Cl− and H+ of the muscle-type ClC chloride channels. J. Gen. Physiol. 118, 23–32 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Estévez, R., Schroeder, B. C., Accardi, A., Jentsch, T. J. & Pusch, M. Conservation of chloride channel structure revealed by an inhibitor binding site in ClC-1. Neuron 38, 47–59 (2003).

    PubMed  Google Scholar 

  30. Engh, A. M. & Maduke, M. Cysteine accessibility in ClC-0 supports conservation of the ClC intracellular vestibule. J. Gen. Physiol. 125, 601–617 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Zifarelli, G. & Pusch, M. ClC chloride channels and transporters: a biophysical and physiological perspective. Rev. Physiol. Biochem. Pharmacol. 158, 23–76 (2007).

    CAS  PubMed  Google Scholar 

  32. Miller, C. ClC chloride channels viewed through a transporter lens. Nature 440, 484–489 (2006).

    CAS  PubMed  Google Scholar 

  33. Jayaram, H., Accardi, A., Wu, F., Williams, C. & Miller, C. Ion permeation through a Cl−-selective channel designed from a ClC Cl−/H+ exchanger. Proc. Natl Acad. Sci. USA 105, 11194–11199 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Walden, M. et al. Uncoupling and turnover in a Cl−/H+ exchange transporter. J. Gen. Physiol. 129, 317–329 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Saviane, C., Conti, F. & Pusch, M. The muscle chloride channel ClC-1 has a double-barreled appearance that is differentially affected in dominant and recessive myotonia. J. Gen. Physiol. 113, 457–468 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Lísal, J. & Maduke, M. The ClC-0 chloride channel is a 'broken' Cl−/H+ antiporter. Nature Struct. Mol. Biol. 15, 805–810 (2008). Using single-channel recordings to show that the gating pattern of ClC-0 channels depends on transmembrane movement of protons, this study firmly established the evolutionary link between ClC pumps and ClC channels and suggested that the channels evolved from a dysfunctional pump.

    Google Scholar 

  37. Gadsby, D. C., Vergani, P. & Csanády, L. The ABC protein turned chloride channel whose failure causes cystic fibrosis. Nature 440, 477–483 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Muallem, D. & Vergani, P. ATP hydrolysis-driven gating in cystic fibrosis transmembrane conductance regulator. Philos. Trans. R. Soc. Lond. B Biol. Sci. 364, 247–255 (2009).

    CAS  PubMed  Google Scholar 

  39. Jordan, K., Kota, K. C., Cui, G., Thompson, C. H. & McCarty, N. A. Evolutionary and functional divergence between the cystic fibrosis transmembrane conductance regulator and related ATP-binding cassette transporter. Proc. Natl Acad. Sci. USA. 105, 18865–18870 (2008).

    CAS  PubMed  Google Scholar 

  40. Vergani, P., Lockless, S. W., Nairn, A. C. & Gadsby, D. C. CFTR channel opening by ATP-driven tight dimerization of its nucleotide-binding domains. Nature 24, 876–880 (2005). This study used CFTR-channel gating kinetics to demonstrate ATP-dependent energetic interaction between residues at positions shown to structurally interact across the interface of prokaryotic nucleotide-binding domain dimers. Evolutionary conservation at these interacting positions in most ABC proteins suggests that nearly all undergo the same ATP-driven cycle of conformational changes established for CFTR.

    Google Scholar 

  41. Nagel, G. et al. Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proc. Natl Acad. Sci. USA 100, 13940–13945 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Richard, E. A. & Miller, C. Steady-state coupling of ion-channel conformations to a transmembrane ion gradient. Science 247, 1208–1210 (1990).

    CAS  PubMed  Google Scholar 

  43. Picollo, A. & Pusch, M. Chloride/proton antiporter activity of mammalian ClC proteins ClC-4 and ClC-5. Nature 436, 420–423 (2005).

    CAS  PubMed  Google Scholar 

  44. Riordan, J. R. et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245, 1066–1073 (1989).

    CAS  PubMed  Google Scholar 

  45. Inagaki, N. et al. Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. Science 270, 1166–1170 (1995).

    CAS  PubMed  Google Scholar 

  46. Hopfner, K. P. et al. Structural biology of Rad50 ATPase: ATP-driven conformational control in DNA double-strand break repair and the ABC-ATPase superfamily. Cell 101, 789–800 (2000). This was the first demonstration that the nucleotide-binding domains of ABC proteins form head-to-tail dimers in the presence of ATP, with one ATP molecule enclosed in each of the two composite catalytic sites formed in the dimer interface. As ADP did not support dimerization, it was proposed that cycles of ATP-induced dimerization and hydrolysis-triggered dissociation provide the basis for function of all ABC proteins.

    CAS  PubMed  Google Scholar 

  47. Sixma, T. K. DNA mismatch repair: MutS structures bound to mismatches. Curr. Opin. Struct. Biol. 11, 47–52 (2001).

    CAS  PubMed  Google Scholar 

  48. Smith, P. C. et al. ATP binding to the motor domain from an ABC transporter drives formation of a nucleotide sandwich dimer. Mol. Cell 10, 139–149 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Lu, G., Westbrooks, J. M., Davidson, A. L. & Chen, J. ATP hydrolysis is required to reset the ATP-binding cassette dimer into the resting-state conformation. Proc. Natl Acad. Sci. USA 102, 17969–17974 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Dawson, R. J. & Locher, K. P. Structure of a bacterial multidrug ABC transporter. Nature 443, 180–185 (2006). This paper reported the first high-resolution structure of an entire ABC transporter that is homologous to clinically relevant human ABC proteins. The structure revealed that the transmembrane helices extend long linker helices into the cytoplasm where they connect to the nucleotide-binding domains via short conserved coupling helices. It also revealed a domain-swapped architecture in which each nucleotide-binding domain receives connections from both N- and C-terminal transmembrane domains.

    CAS  PubMed  Google Scholar 

  51. Dawson, R. J. & Locher, K. P. Structure of the multidrug ABC transporter Sav1866 from Staphylococcus aureus in complex with AMP-PNP. FEBS Lett. 581, 935–938 (2007).

    CAS  PubMed  Google Scholar 

  52. Oldham, M. L., Khare, D., Quiocho, F. A., Davidson, A. L. & Chen, J. Crystal structure of a catalytic intermediate of the maltose transporter. Nature 450, 515–521 (2007).

    CAS  PubMed  Google Scholar 

  53. Ward, A., Reyes, C. L., Yu, J., Roth, C. B. & Chang, G. Flexibility in the ABC transporter MsbA: alternating access with a twist. Proc. Natl Acad. Sci. USA 104, 19005–19010 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Linsdell, P. & Hanrahan, J. W. Adenosine triphosphate-dependent asymmetry of anion permeation in the cystic fibrosis transmembrane conductance regulator chloride channel. J. Gen. Physiol. 111, 601–614 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Kogan, I. et al. CFTR directly mediates nucleotide-regulated glutathione flux. EMBO J. 22, 1981–1989 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Habermann, E. Palytoxin acts through Na+ K+ ATPase. Toxicon 27, 1171–1187 (1989).

    CAS  PubMed  Google Scholar 

  57. Tosteson, M. T. In Seafood and Freshwater: Toxins Pharmacology, Physiology, and Detection (ed. Botana, L. M.) 549–566 (Marcel Dekker, New York, 2000).

    Google Scholar 

  58. Scheiner-Bobis, G., Meyer zu Heringdorf, D., Christ, M. & Habermann, E. Palytoxin induces K+ efflux from yeast cells expressing the mammalian sodium pump. Mol. Pharmacol. 45, 1132–1136 (1994).

    CAS  PubMed  Google Scholar 

  59. Hirsh, J. K. & Wu, C. H. Palytoxin-induced single-channel currents from the sodium pump synthesized by in vitro expression. Toxicon 35, 169–176 (1997).

    CAS  PubMed  Google Scholar 

  60. Artigas, P. & Gadsby, D. C. Large diameter of palytoxin-induced Na/K pump channels and modulation of palytoxin interaction by Na/K pump ligands. J. Gen. Physiol. 123, 357–376 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Artigas, P. & Gadsby, D. C. Na+/K+-pump ligands modulate gating of palytoxin-induced ion channels. Proc. Natl Acad. Sci. USA 100, 501–505 (2003). This study provided support for the view of the Na, K pump as a channel controlled by two gates that open strictly alternately. Current recordings showed that palytoxin interferes with this strict coupling, allowing the two gates to sometimes both be open, but that each gate in a palytoxin-bound pump–channel still responds to its physiological ligand, external K ions or cytoplasmic ATP.

    CAS  PubMed  Google Scholar 

  62. Greie, J. C. & Altendorf, K. The K+-translocating KdpFABC complex from Escherichia coli: a P-type ATPase with unique features. J. Bioenerg. Biomembr. 39, 397–402 (2007).

    CAS  PubMed  Google Scholar 

  63. Reyes, N. & Gadsby, D. C. Ion permeation through the Na+, K+-ATPase. Nature 443, 470–474 (2006).

    CAS  PubMed  Google Scholar 

  64. Takeuchi, A., Reyes, N., Artigas, P., Gadsby, D. C. The ion pathway through the opened Na+, K+-ATPase pump. Nature 456, 413–416 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Gadsby, D. C., Takeuchi, A., Artigas, P. & Reyes, N. Peering into an ATPase ion pump with single-channel recordings. Philos. Trans. R. Soc. Lond. B Biol. Sci. 364, 229–238 (2009).

    CAS  PubMed  Google Scholar 

  66. Accardi, A. et al. Separate ion pathways in a Cl−/H+ exchanger. J. Gen. Physiol. 126, 563–570 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Tzingounis, A. V. & Wadiche, J. I. Glutamate transporters: confining runaway excitation by shaping synaptic transmission. Nature Rev. Neurosci. 8, 935–947 (2007).

    CAS  Google Scholar 

  68. Torres, G. E. & Amara, S. G. Glutamate and monoamine transporters: new visions of form and function. Curr. Opin. Neurobiol. 17, 304–312 (2007).

    CAS  PubMed  Google Scholar 

  69. Gouaux, E. The molecular logic of sodium-coupled neurotransmitter transporters. Philos. Trans. R. Soc. Lond. B Biol. Sci. 364, 149–154 (2009).

    CAS  PubMed  Google Scholar 

  70. Fairman, W. A., Vandenberg, R. J., Arriza, J. L., Kavanaugh, M. P. & Amara, S. G. An excitatory amino-acid transporter with properties of a ligand-gated chloride channel. Nature 375, 599–603 (1995).

    CAS  PubMed  Google Scholar 

  71. Larsson, H. P., Picaud, S. A., Werblin, F. S. & Lecar, H. Noise analysis of the glutamate-activated current in photoreceptors. Biophys. J. 70, 733–742 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Wadiche, J. I. & Kavanaugh, M. P. Macroscopic and microscopic properties of a cloned glutamate transporter/chloride channel. J. Neurosci. 18, 7650–7661 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Ryan, R. M. & Mindell, J. A. The uncoupled chloride conductance of a bacterial glutamate transporter homolog. Nature Struct. Mol. Biol. 14, 365–371 (2007). This study used reconstituted purified glutamate transporter protein to establish that the uncoupled channel-like Cl current flows through the same protein that carries out stoichiometric Na-dependent transport of glutamate.

    CAS  Google Scholar 

  74. Vandenberg, R. J., Huang, S. & Ryan, R. M. Slips, leaks and channels in glutamate transporters. Channels 2, 51–58 (2008).

    PubMed  Google Scholar 

  75. Ryan, R. M., Mitrovic, A. D. & Vandenberg, R. J. The chloride permeation pathway of a glutamate transporter and its proximity to the glutamate translocation pathway. J. Biol. Chem. 279, 20742–20751 (2004).

    CAS  PubMed  Google Scholar 

  76. Otis, T. S. & Kavanaugh, M. P. Isolation of current components and partial reaction cycles in the glial glutamate transporter EAAT2. J. Neurosci. 20, 2749–2757 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Post, R. L. & Jolly, P. C. The linkage of sodium, potassium, and ammonium active transport across the human erythrocyte membrane. Biochim. Biophys. Acta 25, 118–128 (1957).

    CAS  PubMed  Google Scholar 

  78. Jørgensen P. L. Isolation of (Na+ plus K+)-ATPase. Methods Enzymol. 32, 277–290 (1974).

    PubMed  Google Scholar 

  79. Gadsby, D. C., Kimura, J. & Noma, A. Voltage dependence of Na/K pump current in isolated heart cells. Nature 315, 63–65 (1985).

    CAS  PubMed  Google Scholar 

  80. Nakao, M. & Gadsby, D. C. Voltage dependence of Na translocation by the Na/K pump. Nature 323, 628–630 (1986).

    CAS  PubMed  Google Scholar 

  81. Artigas, P. & Gadsby, D. C. Ion channel-like properties of the Na+/K+ pump. Ann. NY Acad. Sci. 976, 31–40 (2002).

    CAS  PubMed  Google Scholar 

  82. Simons, T. J. B. The interaction of ATP-analogues possessing a blocked γ-phosphate group with the sodium pump in human red cells. J. Physiol. 244, 731–739 (1975).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Forbush, B. 3rd. Rapid release of 42K and 86Rb from an occluded state of the Na, K-pump in the presence of ATP or ADP. J. Biol. Chem. 244, 731–739 (1987).

    Google Scholar 

  84. Gadsby D. C. Ion transport: spot the difference. Nature 427, 795–797 (2004).

    CAS  PubMed  Google Scholar 

  85. Lobet, S. & Dutzler, R. Ion-binding properties of the CIC chloride selectivity filter. EMBO J. 25, 24–33 (2006).

    CAS  PubMed  Google Scholar 

  86. Dutzler, R. A structural perspective on CIC channel and transporter function. FEBS Letters 581, 2839–2844 (2007).

    CAS  PubMed  Google Scholar 

  87. Mornon, J. P., Lehn, P. & Callebaut, I. Atomic model of human cystic fibrosis transmembrane conductance regulator: membrane-spanning domains and coupling interfaces. Cell. Mol. Life Sci. 65, 2594–2612 (2008).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

I thank present and past laboratory members for their contributions to the research and ideas encapsulated here, A. Takeuchi, A. Gulyás-Kovács, P. Vergani, P. Artigas and P. Hoff for help with figures, R. Dutzler and R. MacKinnon for images and the National Institutes of Health for funding via grants HL36783, HL49907 and DK51767.

Author information

Authors and Affiliations

  1. Laboratory of Cardiac/Membrane Physiology, The Rockefeller University, 1230 York Avenue, New York, 10065-6399, New York, USA

    David C. Gadsby

Authors
  1. David C. Gadsby
    View author publications

    You can also search for this author inPubMed Google Scholar

Related links

Related links

FURTHER INFORMATION

David C. Gadsby's homepage

Transport Classification Database

Glossary

Membrane potential

The difference in electrical potential between one side of a membrane and the other; usually the electrical potential inside a cell measured with respect to that of the extracellular space.

Activation gate

A gate in an ion channel that when opened initiates ion flow through the channel pore.

Gating reaction

A change in the conformation of a transmembrane transport protein that alters access to the substrate translocation pathway.

Selectivity filter

The narrow region of an ion translocation pathway in which the transport protein interacts with the ions to select among them on the basis of their physicochemical characteristics.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gadsby, D. Ion channels versus ion pumps: the principal difference, in principle. Nat Rev Mol Cell Biol 10, 344–352 (2009). https://doi.org/10.1038/nrm2668

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm2668

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing