Skip to main content
SpringerLink
Log in

Electrophysiological Measurements of Membrane Proteins

  • Chapter
  • First Online:
Fundamental Concepts in Biophysics

Part of the book series: Handbook of Modern Biophysics ((HBBT))

Ion channels and transporters are macromolecular proteins in the cell membrane that consist of ion transport pathways in the protein structure. These membrane proteins catalyze ion flux across lipid membranes and thus generate currents that flow into or out of cells. By altering electric currents through cell membranes, ion channels and transporters control the membrane potential, an important property of living cells [1]. In addition, the ions that flow into cells (for example, Ca2+ ions) may play significant roles as intracellular messengers, and thus are critical for signal transduction mechanisms in cells [2]. A defect in ion transport can result in a variety of cellular malfunctions that cause many human diseases [3].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Further Study

  • Hille, B. 2001. Ion channels of excitable membranes. Sunderland, MA: Sinauer Associates.

    Google Scholar 

  • Sakmann B, Neher E. 1983. Single-channel recording, 1st ed. New York: Plenum.

    Google Scholar 

  • Sakmann B, Neher E. Single-channel recording, 2nd ed. New York: Plenum.

    Google Scholar 

  • Waltz W, Boulton A, Baker G, eds. 2002. Patch-clamp analysis. Totowa, NJ: Humana.

    Book  Google Scholar 

  • Ashcroft F. 2000. Ion channels and diseases: channelopathies. London: Academic.

    Google Scholar 

  • Lakowicz J. 2006. Principles of fluorescence spectroscopy. 3rd ed. New York: Springer.

    Book  Google Scholar 

References

  1. Hille B. 2001. Ion channels of excitable membranes. Sunderland, MA: Sinauer Associates.

    Google Scholar 

  2. Means A, ed. 1998. Calcium regulation of cellular function. San Diego: Academic Press.

    Google Scholar 

  3. Ashcroft F. 2000. Ion channels and diseases: channelopathies. London: Academic Press.

    Google Scholar 

  4. Siegelbaum S, Koester J. 2000. Ion channels. In Principles of neural science, pp. 105–24. Ed E Kandel, J Schwartz T Jessell. New York: McHraw-Hill.

    Google Scholar 

  5. Nicholls J, Martin A, Wallace B, Fuchs P. 2001. From neuron to brain, 4th ed. Sunderland, MA: Sinauer Associates.

    Google Scholar 

  6. Sperelakis N. 2001. Electrogenesis of membrane excitability. In Cell physioloy sourcebook, pp. 417–439. Ed N Sperelakis. San Diego: Academic Press.

    Google Scholar 

  7. Koester J, Siegelbaum S. 2000. Local signaling: passive electrical properties of the neuron. In Principles of neural science, pp. 140–149. New York: McGraw-Hill.

    Google Scholar 

  8. Sperelakis N. 2001. Cable properties and propagation of action potentials. In Cell physiology sourcebook, pp. 395–406. Ed N Sperelakis. San Diego: Academic Press.

    Google Scholar 

  9. Neher E, Sakmann B. 1976. Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature 260(5554):799–802.

    Article  ADS  Google Scholar 

  10. Posson DJ, Ge P, Miller C, Bezanilla F, Selvin PR. 2005. Small vertical movement of a K+ channel voltage sensor measured with luminescence energy transfer. Nature 436(7052):848–851.

    Article  ADS  Google Scholar 

  11. Zagotta WN, Hoshi T, Aldrich RW. 1994. Shaker potassium channel gating, III: evaluation of kinetic models for activation. J Gen Physiol 103(2):321–362.

    Article  Google Scholar 

  12. Ma Z, Lou XJ, Horrigan FT. 2006. Role of charged residues in the S1–S4 voltage sensor of BK channels. J Gen Physiol 127(3):309–328.

    Article  Google Scholar 

  13. Lee WY, Sine SM. 2004. Invariant aspartic acid in muscle nicotinic receptor contributes selectively to the kinetics of agonist binding. J Gen Physiol 124(5):555–567.

    Article  Google Scholar 

  14. Hwang TC, Nagel G, Nairn AC, Gadsby DC. 1994. Regulation of the gating of cystic fibrosis transmembrane conductance regulator C1 channels by phosphorylation and ATP hydrolysis. Proc Natl Acad Sci USA 91(11):4698–4702.

    Article  ADS  Google Scholar 

  15. Chen S, Wang J, Zhou L, George MS, Siegelbaum SA. 2007. Voltage sensor movement and cAMP binding allosterically regulate an inherently voltage-independent closed-open transition in HCN channels. J Gen Physiol 129(2):175–88.

    Article  Google Scholar 

  16. Colquhoun D, Hawkes A. 1983. The priciples of the stochastic interpretation of ion-channel mechanisms. In Single-channel recording, pp. 135–175. Ed B Sakmann, E Neher. New York: Plenum.

    Google Scholar 

  17. Aldrich R, Yellen G. 1983. Analysis of nonstationary channel kinetics. In Single-channel recording, pp. 187–299. Ed B Sakmann, E Neher. New York: Plenum.

    Google Scholar 

  18. Heginbotham L, Abramson T, MacKinnon R. 1992. A functional connection between the pores of distantly related ion channels as revealed by mutant K+ channels. Science 258(5085):1152–1155.

    Article  ADS  Google Scholar 

  19. Qu W, Moorhouse AJ, Chandra M, Pierce KD, Lewis TM, Barry PH. 2006. A single P-loop glutamate point mutation to either lysine or arginine switches the cation–anion selectivity of the CNGA2 channel. J Gen Physiol 127(4):375–389.

    Article  Google Scholar 

  20. Zhang XD, Li Y, Yu WP, Chen TY. 2006. Roles of K149, G352, and H401 in the channel functions of C1C-0: testing the predictions from theoretical calculations. J Gen Physiol 127(4):435–447.

    Article  Google Scholar 

  21. Hodgkin AL, Keynes RD. 1955. The potassium permeability of a giant nerve fibre. J Physiol 128(1):61–88.

    Google Scholar 

  22. Coronado R, Rosenberg RL, Miller C. 1980. Ionic selectivity, saturation, and block in a K+-selective channel from sarcoplasmic reticulum. J Gen Physiol 76(4):425–446.

    Article  Google Scholar 

  23. Lauger P. 1973. Ion transport through pores: a rate-theory analysis. Biochim Biophys Acta 311(3):423–441.

    Article  Google Scholar 

  24. Doyle DA, Morais Cabral J, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R. 1998. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280(5360):69–77.

    Article  ADS  Google Scholar 

  25. Kuo CC, Hess P. 1993. Ion permeation through the L-type Ca2+ channel in rat phaeochromocytoma cells: two sets of ion binding sites in the pore. J Physiol 466:629–655.

    Google Scholar 

  26. Yang J, Ellinor PT, Sather WA, Zhang JF, Tsien RW. 1993. Molecular determinants of Ca2+ selectivity and ion permeation in L-type Ca2+ channels. Nature 366(6451):158–161.

    Article  ADS  Google Scholar 

  27. Almers W, McCleskey EW. 1984. Non-selective conductance in calcium channels of frog muscle: calcium selectivity in a single-file pore. J Physiol 353:585–608.

    Google Scholar 

  28. Hess P, Tsien RW. 1984. Mechanism of ion permeation through calcium channels. Nature 309(5967):453–456.

    Article  ADS  Google Scholar 

  29. Nonner W, Eisenberg B. 1998. Ion permeation and glutamate residues linked by Poisson-Nernst-Planck theory in L-type calcium channels. Biophys J 75(3):1287–1305.

    Article  Google Scholar 

  30. Nonner W, Chen DP, Eisenberg B. 1999. Progress and prospects in permeation. J Gen Physiol 113(6):773–782.

    Article  Google Scholar 

  31. Miller C. 1999. Ionic hopping defended. J Gen Physiol 113(6):783–787.

    Article  Google Scholar 

  32. Stuhmer W, Parekh A. 1995. Electrophysiological recordings from Xenopus oocytes. In Single-channel recording, 2nd ed, pp. 341–356. Ed B Sakmann, E Neher. New York: Plenum.

    Google Scholar 

  33. Dumont JN. 1972. Oogenesis in Xenopus laevis (Daudin), I: stages of oocyte development in laboratory maintained animals. J Morphol 136(2):153–179.

    Article  Google Scholar 

  34. Biskup C, Kusch J, Schulz E, Nache V, Schwede F, Lehmann F, Hagen V, Benndorf K. 2007. Relating ligand binding to activation gating in CNGA2 channels. Nature 446(7134):440–443.

    Article  ADS  Google Scholar 

  35. Sigworth FJ, Neher E. 1980. Single Na+ channel currents observed in cultured rat muscle cells. Nature 287(5781):447–449.

    Article  ADS  Google Scholar 

  36. Neher E. 1982. Unit conductance studies in biological membranes. In Techniques in cellular physiology, pp. 1–16. Ed P Baker. Amsterdam: Elsevier.

    Google Scholar 

  37. Heinemann SH. 1995. Guide to data acquisition and analysis. In Single-channel recording, 2nd ed, pp. 53–91. Ed B Sakmann, E Neher. New York: Plenum.

    Google Scholar 

  38. Levis R, Rae JL. 2002. Technology of patch-clamp electrodes. In Patch-clamp analysis, pp. 1–34. Ed W Waltz, A Boulton, G Baker. Totowa, NJ: Humana Press.

    Google Scholar 

  39. Penner R. 1995. A practical guide to patch clamping. In Single-channel recordings, 2nd ed, pp. 3–30. Ed B Sakmann, E Neher. New York: Plenum.

    Google Scholar 

  40. Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ. 1981. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch 391(2):85–100.

    Article  Google Scholar 

  41. Soejima M, Noma A. 1984. Mode of regulation of the ACh-sensitive K-channel by the muscarinic receptor in rabbit atrial cells. Pflugers Arch 400(4):424–431.

    Article  Google Scholar 

  42. Neher E, Eckert R. 1988. Fast patch-pipette internal perfusion with minimum solution flow. In Calcium and ion channel modulation, pp. 371–377. Ed A Grinnell, D Armstrong, M Jackson M. New York: Plenum.

    Google Scholar 

  43. Tang JM, Wang J, Quandt FN, Eisenberg RS. 1990. Perfusing pipettes. Pflugers Arch 416(3):347–350.

    Article  Google Scholar 

  44. Horn R, Marty A. 1988. Muscarinic activation of ionic currents measured by a new whole-cell recording method. J Gen Physiol 92(2):145–159.

    Article  Google Scholar 

  45. Rae J, Cooper K, Gates P, Watsky M. 1991. Low access resistance perforated patch recordings using amphotericin B. J Neurosci Methods 37(1):15–26.

    Article  Google Scholar 

  46. Zhou Z, Neher E. 1993. Mobile and immobile calcium buffers in bovine adrenal chromaffin cells. J Physiol 469:245–73.

    Google Scholar 

  47. Hilgemann DW. 1989. Giant excised cardiac sarcolemmal membrane patches: sodium and sodium-calcium exchange currents. Pflugers Arch 415(2):247–249.

    Article  Google Scholar 

  48. Macdonald RL, Olsen RW. 1994. GABAA receptor channels. Annu Rev Neurosci 17:569–602.

    Google Scholar 

  49. Chen C, Okayama H. 1987. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol 7(8):2745–2752.

    Google Scholar 

  50. McManus OB, Magleby KL. 1988. Kinetic states and modes of single large-conductance calcium-activated potassium channels in cultured rat skeletal muscle. J Physiol 402:79–120.

    Google Scholar 

  51. Lin YF, Browning MD, Dudek EM, Macdonald RL. 1994. Protein kinase C enhances recombinant bovine alpha 1 beta 1 gamma 2L GABAA receptor whole-cell currents expressed in L929 fibroblasts. Neuron 13(6):1421–1431.

    Article  Google Scholar 

  52. Greenfield Jr LJ, Macdonald RL. 1996. Whole-cell and single-channel alpha1 beta1 gamma2S GABAA receptor currents elicited by a “multipuffer” drug application device. Pflugers Arch 432(6):1080–1090.

    Article  Google Scholar 

  53. Babenko AP, Aguilar-Bryan L, Bryan J. 1998. A view of sur/KIR6.X, KATP channels. Annu Rev Physiol 60:667–687.

    Article  Google Scholar 

  54. Seino S, Miki T. 2003. Physiological and pathophysiological roles of ATP-sensitive K+ channels. Prog Biophys Mol Biol 81(2):133–176.

    Article  Google Scholar 

  55. Quayle JM, Bonev AD, Brayden JE, Nelson MT. 1994. Calcitonin gene-related peptide activated ATP-sensitive K+ currents in rabbit arterial smooth muscle via protein kinase A. J Physiol 475(1):9–13.

    Google Scholar 

  56. Hatakeyama N, Wang Q, Goyal RK, Akbarali HI. 1995. Muscarinic suppression of ATP-sensitive K+ channel in rabbit esophageal smooth muscle. Am J Physiol 268(4 Pt 1):C877–C885.

    Google Scholar 

  57. Sigworth FJ, Sine SM. 1987. Data transformations for improved display and fitting of single-channel dwell time histograms. Biophys J 52(6):1047–1054.

    Article  Google Scholar 

  58. Horn R. 1987. Statistical methods for model discrimination: applications to gating kinetics and permeation of the acetylcholine receptor channel. Biophys J 51(2):255–263.

    Article  Google Scholar 

  59. Colquhoun D, Sakmann B. 1985. Fast events in single-channel currents activated by acetylcholine and its analogues at the frog muscle end-plate. J Physiol 369:501–557.

    Google Scholar 

  60. Lin YF, Jan YN, Jan LY. 2000. Regulation of ATP-sensitive potassium channel function by protein kinase A-mediated phosphorylation in transfected HEK293 cells. EMBO J 19(5):942–955.

    Article  Google Scholar 

  61. Zheng J. 2006. Patch fluorometry: shedding new light on ion channels. Physiology (Bethesda) 21:6–12.

    Google Scholar 

  62. Zheng J, Zagotta WN. 2003. Patch-clamp fluorometry recording of conformational rearrangements of ion channels. Sci STKE 2003(176):PL7.

    Article  Google Scholar 

  63. Trudeau MC, Zagotta WN. 2004. Dynamics of Ca2+-calmodulin-dependent inhibition of rod cyclic nucleotidegated channels measured by patch-clamp fluorometry. J Gen Physiol 124(3):211–223.

    Article  Google Scholar 

  64. Zheng J, Zagotta WN. 2000. Gating rearrangements in cyclic nucleotide-gated channels revealed by patch-clamp fluorometry. Neuron 28(2):369–374.

    Article  Google Scholar 

  65. Mansoor SE, McHaourab HS, Farrens DL. 2002. Mapping proximity within proteins using fluorescence spectroscopy: a study of T4 lysozyme showing that tryptophan residues quench bimane fluorescence. Biochemistry 41(8):2475–2484.

    Article  Google Scholar 

  66. Islas LD, Zagotta WN. 2006. Short-range molecular rearrangements in ion channels detected by tryptophan quenching of bimane fluorescence. J Gen Physiol 128(3):337–346.

    Article  Google Scholar 

  67. Lakowicz J. 2006. Principles of fluorescence spectroscopy. New York: Springer.

    Book  Google Scholar 

  68. Cheng W, Yang F, Takanishi CL, Zheng J. 2007. Thermosensitive TRPV channel subunits coassemble into heteromeric channels with intermediate conductance and gating properties. J Gen Physiol 129(3):191–207.

    Article  Google Scholar 

  69. Staruschenko A, Medina JL, Patel P, Shapiro MS, Booth RE, Stockand JD. 2004. Fluorescence resonance energy transfer analysis of subunit stoichiometry of the epithelial Na+ channel. J Biol Chem 279(26):27729–27734.

    Article  Google Scholar 

  70. Zheng J, Trudeau MC, Zagotta WN. 2002. Rod cyclic nucleotide-gated channels have a stoichiometry of three CNGA1 subunits and one CNGB1 subunit. Neuron 36(5):891–896.

    Article  Google Scholar 

  71. Zheng J, Zagotta WN. 2004. Stoichiometry and assembly of olfactory cyclic nucleotide-gated channels. Neuron 42(3):411–421.

    Article  Google Scholar 

  72. Weitz D, Ficek N, Kremmer E, Bauer PJ, Kaupp UB. 2002. Subunit stoichiometry of the CNG channel of rod photoreceptors. Neuron 36(5):881–889.

    Article  Google Scholar 

  73. Zhong H, Molday LL, Molday RS, Yau KW. 2002. The heteromeric cyclic nucleotide-gated channel adopts a 3A:1B stoichiometry. Nature 420(6912):193–198.

    Article  ADS  Google Scholar 

  74. Bykova EA, Zhang XD, Chen TY, Zheng J. 2006. Large movement in the C terminus of CLC-0 chloride channel during slow gating. Nat Struct Mol Biol 13(12):1115–1119.

    Article  Google Scholar 

  75. Cha A, Snyder GE, Selvin PR, Bezanilla F. 1999. Atomic scale movement of the voltage-sensing region in a potassium channel measured via spectroscopy. Nature 402(6763):809–813.

    Article  ADS  Google Scholar 

  76. Glauner KS, Mannuzzu LM, Gandhi CS, Isacoff EY. 1999. Spectroscopic mapping of voltage sensor movement in the Shaker potassium channel. Nature 402(6763):813–817.

    Article  ADS  Google Scholar 

  77. Chanda B, Asamoah OK, Blunck R, Roux B, Bezanilla F. 2005. Gating charge displacement in voltage-gated ion channels involves limited transmembrane movement. Nature 436(7052):852–856.

    Article  ADS  Google Scholar 

  78. Zheng J, Varnum MD, Zagotta WN. 2003. Disruption of an intersubunit interaction underlies Ca2+-calmodulin modulation of cyclic nucleotide-gated channels. J Neurosci 23(22):8167–8175.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Neuroscience, University of California, Davis,

    Tsung-Yu Chen

  2. Departments of Neurology, University of California, Davis,

    Tsung-Yu Chen

  3. Anesthesiology,, University of California, Davis,

    Yu-Fung Lin

  4. Physiology and Membrane Biology, University of California, Davis,

    Yu-Fung Lin & Jie Zheng

Authors
  1. Tsung-Yu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu-Fung Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jie Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

    Rights and permissions

    Reprints and permissions

    Copyright information

    © 2009 Humana Press

    About this chapter

    Cite this chapter

    Chen, TY., Lin, YF., Zheng, J. (2009). Electrophysiological Measurements of Membrane Proteins. In: Jue, T. (eds) Fundamental Concepts in Biophysics. Handbook of Modern Biophysics. Humana Press. https://doi.org/10.1007/978-1-59745-397-4_5

    Download citation

    Publish with us

    Policies and ethics

    Search

    Navigation