Introduction to Ion Channels

  • Chiara Di Resta
  • Andrea Becchetti
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 674)


Ion channels are integral membrane proteins that contain pathways through which ions can flow. By shifting between closed and open conformational states (‘gating’ process), they control passive ion flow through the plasma membrane. Channels can be gated by membrane potential, or specific ligands, or other agents, such as mechanical stimuli. The efficacy of the gating process and the kinetics of subsequent inactivation or desensitization are regulated by intracellular mechanisms. Many types of membrane channels exist, with different degrees of ion selectivity. By controlling ion fluxes, they typically regulate membrane potential and excitability, shape the action potential, trigger muscle contraction and exocytosis (through Ca2+ influx), regulate cell volume and many other cellular processes. In the first part of the chapter, we give a brief introduction to the main physiological aspects of ion channels, which may not be familiar to molecular biologists. Subsequently, as a reference for later chapters, we summarize the main structural and functional features of the channel-proteins presently known to be related to integrin receptors.


Channel Type Idiopathic Generalize Epilepsy Versus Channel HERG Current Neuronal nAChRs 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Hodgkin AL, Huxley AF. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol 1952; 117:500–544.PubMedGoogle Scholar
  2. 2.
    Skou JC. The influence of some cations on an adenosine triphosphatase from peripheral nerves. Biochem Biophys Acta 1957; 23:394–401.CrossRefPubMedGoogle Scholar
  3. 3.
    Eccles JC. The physiology of synapses. New York: Academic Press, 1964.Google Scholar
  4. 4.
    Katz B. The release of neural transmitter substances. Liverpool University Press, 1969.Google Scholar
  5. 5.
    Conti F, Wanke E. Channel noise in nerve membranes and lipid bilayers. Q Rev Biophys 1975; 8:451–506.CrossRefPubMedGoogle Scholar
  6. 6.
    Robinson JD. Mechanisms of Synaptic Transmission. Bridging the Gaps (1890–1990). Oxford University Press, 2001.Google Scholar
  7. 7.
    Noda M, Takahashi H, Tanabe T et al. Primary structure of the α-subunit precursor of Torpedo californica acetylcholine receptor deduced from cDNA sequence. Nature 1982; 299:793–797.CrossRefPubMedGoogle Scholar
  8. 8.
    Doyle DA, Morais-Cabral J, Pfuetzner RA et al. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 1998; 280:69–77.CrossRefPubMedGoogle Scholar
  9. 9.
    Dutzler R, Campbell EB, Cadene M et al. X-ray structure of a CLC chloride channel at 3.0 Å reveals the molecular basis of anion selectivity. Nature 2002; 415:287–294.CrossRefPubMedGoogle Scholar
  10. 10.
    Neher E, Sakmann B. Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature 1976; 260:799–802.CrossRefPubMedGoogle Scholar
  11. 11.
    Hamill OP, Marty E, Neher B et al. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Arch 1981; 391:85–100.CrossRefPubMedGoogle Scholar
  12. 12.
    Aidley DJ, The Physiology of Excitable Cells, 3rd Ed. Cambridge University Press, 1998.Google Scholar
  13. 13.
    Blaustein MP, Kao JPY, Matteson DR. Cellular Physiology. Elsevier Inc, 2004Google Scholar
  14. 14.
    Johnston D, Wu SM. Foundations of cellular neurophysiology. MIT Press 1995.Google Scholar
  15. 15.
    Hille B. Ion channels of excitable membranes. Sinauer Associates 2001.Google Scholar
  16. 16.
    Somjen GC. Ions in the Brain: Normal Function, Seizures and Stroke. Oxford University Press, 2004.Google Scholar
  17. 17.
    Ben-Ari Y, Gaiarsa JL, Tyzio R et al. GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations. Physiol Rev 2007; 87:1215–1284.CrossRefPubMedGoogle Scholar
  18. 18.
    Gutman GA, Chandy KG, Grissmer S et al. International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels. Pharmacol Rev 2005; 57:473–508.CrossRefPubMedGoogle Scholar
  19. 19.
    McKinnon R, Yellen G. Mutations affecting TEA blockade and ion permeation in voltage-activated K+ channels. Science 1990; 250:276–279.CrossRefGoogle Scholar
  20. 20.
    Yool AJ, Schwartz TL. Alteration of ionic selectivity of a K+ channel. Nature 1991; 349:700–704.CrossRefPubMedGoogle Scholar
  21. 21.
    Bucossi G, Eismann E, Sesti F et al. Time-dependent current decline in cyclic GMP-gated bovine channels caused by point mutations in the pore region expressed in Xenopus oocytes. J Physiol 1996; 493:409–441.PubMedGoogle Scholar
  22. 22.
    Becchetti A, Gamel K, Torre V. Cyclic nucleotide-gated channels. Pore topology studied through the accessibility of reporter cysteines. J Gen Physiol 1999; 114:377–392.CrossRefPubMedGoogle Scholar
  23. 23.
    Liu J, Siegelbaum SA. Change of pore helix conformational state upon opening of cyclic nucleotide-gated channels. Neuron 2000; 28:899–909.CrossRefPubMedGoogle Scholar
  24. 24.
    Chittajallu R, Chen Y, Wang H et al. Regulation of Kv1 subunit expression in oligodendrocyte progenitor cells and their role in G1/S phase progression of the cell cycle. Proc Natl Acad Sci USA 2002; 99:2350–2355.CrossRefPubMedGoogle Scholar
  25. 25.
    Zhou M, Kimelberg HK. Freshly isolated astrocytes from rat hippocampus show two distinct current patterns and different [K+]o uptake capabilities. J Neurophysiol 2000; 84:2746–2757.PubMedGoogle Scholar
  26. 26.
    Smith PL, Baukrowitz T, Yellen G. The inward rectification mechanism of the HERG cardiac potassium channel. Nature 1996; 379:833–836.CrossRefPubMedGoogle Scholar
  27. 27.
    Sanguinetti MC, Tristani-Firouzi P. hERG potassium channels and cardiac arrhythmia. Nature 2006; 440:463–469.CrossRefPubMedGoogle Scholar
  28. 28.
    Guasti L, Cilia E, Crociani O et al. Expression pattern of the Ether-á-go-go-related (ERG) family proteins in the adult mouse central nervous system: evidence for coassembly of different subunits. J Comp Neurol 2005; 491:157–174.CrossRefPubMedGoogle Scholar
  29. 29.
    Arcangeli A, Becchetti A. Ion channels and the cell cycle. In: D. Janigro, ed. The Cell Cycle in the Nervous Central System. Hartford: Humana Press, 2006.Google Scholar
  30. 30.
    Morais Cabral JH, Lee A, Cohen SL et al. Crystal structure and functional analysis of the HERG potassium channel N terminus: a eukaryotic PAS domain. Cell 1998; 95:649–655.CrossRefPubMedGoogle Scholar
  31. 31.
    London B, Trudeau MC, Newton KP et al. Two isoforms of the mouse ether-á-go-go-related gene coassemble to form channels with properties similar to the rapidly activating component of the cardiac delayed rectifier K+ current. Circ Res 1997; 81:870–878.PubMedGoogle Scholar
  32. 32.
    Crociani O, Guasti L, Balzi M et al. Cell cycle-dependent expression of HERG1 and HERG1b isoforms in tumor cells. J Biol Chem 2003; 278:2947–2955.CrossRefPubMedGoogle Scholar
  33. 33.
    Lu Z. Mechanisms of rectification in inward-rectifier K+ channels. Annu Rev Physiol 2004; 66:103–129.CrossRefPubMedGoogle Scholar
  34. 34.
    Nichols CG, Lopatin AN. Inward rectifier potassium channels. Annu Rev Physiol 1997; 59:171–191.CrossRefPubMedGoogle Scholar
  35. 35.
    Kubo Y, Adelman JP, Clapham DE et al. International Union of Pharmacology. LIV nomenclature and molecular relationships of inwardly rectifying potassium channels. Pharmacol Rev 2005; 57:509–526.CrossRefPubMedGoogle Scholar
  36. 36.
    Stocker M. Ca2+-activated K+ channels: molecular determinants and function of the SK family. Nat Rev Neurosci 2004; 5:758–770.CrossRefPubMedGoogle Scholar
  37. 37.
    Salkoff L, Butler A, Ferreira G et al. High-conductance potassium channels of the SLO family. Nat Rev Neurosci 2006; 5:921–931.CrossRefGoogle Scholar
  38. 38.
    Wei AD, Gutman GA, Aldrich R et al. International Union of Pharmacology. LII nomenclature and molecular relationships of calcium-activated potassium channels. Pharmacol Rev 2005; 57:463–472.CrossRefPubMedGoogle Scholar
  39. 39.
    Khosravani H, Zamponi GW. Voltage-gated calcium channels and idiopathic generalized epilepsies. Physiol Rev 2006; 86:941–966.CrossRefPubMedGoogle Scholar
  40. 40.
    Catterall WA, Perez-Royes E, Snutch TP et al. International Union of Pharmacology. XLVIII nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol Rev 2005; 57:411–425.CrossRefPubMedGoogle Scholar
  41. 41.
    Chen T-Y. Structure and function of CLC channels. Annu Rev Physiol 2005; 67:809–839.CrossRefPubMedGoogle Scholar
  42. 42.
    Hartzell C, Putzier I, Arreola J. Calcium-activated chloride channels. Annu Rev Physiol 2005; 67:719–758.CrossRefPubMedGoogle Scholar
  43. 43.
    Abdel-Ghany M, Cheng H-C, Eible RC et al. Focal adhesion kinase activated by β4 integrin ligation to mCLCA1 mediates early metastatic growth. J Biol Chem 2002; 277:34391–34400.CrossRefPubMedGoogle Scholar
  44. 44.
    Gotti C, Clementi F. Neuronal nicotinic receptors: from structure to pathology. Prog Neurobiol 2004; 74:363–396.CrossRefPubMedGoogle Scholar
  45. 45.
    Dani JA, Bertrand D. Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system. Annu Rev Pharmacol Toxicol 2007; 47:699–729.CrossRefPubMedGoogle Scholar
  46. 46.
    Mayer ML, Armstrong N. Structure and function of glutamate receptor ion channels. Annu Rev Physiol 2004; 66:161–181.CrossRefPubMedGoogle Scholar
  47. 47.
    Mayer ML. Glutamate receptor ion channels. Curr Opin Neurobiol 2005; 15:282–288.CrossRefPubMedGoogle Scholar
  48. 48.
    Nedergaard M, Takano T, Hansen AJ. Beyond the role of glutamate as a neurotransmitter. Nat Rev Neurosci 2002; 3:748–753.CrossRefPubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  1. 1.Department of Biotechnology and BiosciencesUniversity of Milano-BicoccaMilanoItaly

Personalised recommendations