Ion Channels


Ion channels are membrane proteins that create specialised routes for ions to cross cell membrane lipid bilayers selectively, and at relatively high speeds. All cells of all organisms use ion channels of different types to control a range of functions. The majority of electrical membrane signals originate from the flow of select types of ions through ion channels. Cellular control of ion channel activity is critical for singleā€cell and multicellular organisms to respond to their environments. Avoiding external threats, seeking nutrients, adapting to normal developmental processes, creating memories and modifying outputs according to previous events all involve ion channel activity. Ion channel dysfunction underlies multiple human disorders and diseases. Developmental disorders, pain syndromes that include extreme pain as well as congenital indifference to pain, certain types of migraines, epilepsies, ataxias, paralyses, cardiac arrhythmias and renal failure can all be due to malfunctioning ion channels. Thus, ion channels are critically important drug targets for the treatment of many illnesses and disorders.

Key Concepts:

  • Ion channels are found in all living cells.

  • Ion channels create specialised routes for ions to cross biological cell membranes.

  • Ion channels support the rapid flow of ions across biological membranes to generate electrical membrane signalling.

  • Ion channels are gated (opened and closed) by a wide range of biological signals.

  • Ion channels are selectively permeable to specific ions.

  • Certain ion channels control the influx of calcium, a critical intracellular second messenger.

  • A range of extracellular, intracellular and membrane signals alter the activity of ion channels.

  • Abnormal ion channel function underlies many disorders and diseases.

  • Ion channels are important targets of drugs and toxins.

Keywords: electrical signalling; neurons; ion transport; ion permeation; membrane proteins; ion channelopathies; disease; drugs

Figure 1.

View of an ion channel within the cell membrane. The lipid bilayer is shown surrounding the ion channel protein complex. The location of the ion pore that spans the membrane lies in the central axis formed by the assembly of four subunits (right). One of the four subunits has been removed to reveal the central ion pore with two ions located in the narrow part of the selectively filter and ions entering the vestibules at the inner and outer mouths of the ion channel pore (left). This ion channel is a tetramer which is the basic structure of voltage‐gated ion channels. Artwork by Kelly L McGuire and Diane Lipscombe.

Figure 2.

The approximate time course and magnitude of the change in membrane potential in an excitable cell during an action potential waveform. The value of the membrane potential is shown on the y‐axis and time on the x‐axis. During the action potential waveform the value of the cell membrane potential rapidly sweeps from −70 to +40 mV and then returns to −70 mV within 1–2 ms. The relative permeabilities of the cell membrane to potassium (PK) and sodium (PNa) are indicated at the start (1), peak (2), the most negative value following repolarisation (3) and then sometime after the membrane potential returns to rest (1). Artwork by Kelly L. McGuire and Diane Lipscombe.

Figure 3.

Single‐channel currents recorded using the patch clamp technique. Examples of currents recorded from single NMDA receptor cation channels (top) and GABAA receptor Cl channels (bottom). Currents were recorded in outside‐out patches of cell membrane. The positions of closed (C) and open (O1, O2) levels are shown. The amount of current that flows through the channel is the same at a given membrane potential. The agonist used to activate NMDA receptors is 1 mM glutamate plus 1 mM glycine (required cofactor; upper recordings). The agonist used to activate GABAB receptors is 100 μM GABA (lower recordings). In both sets of recordings the net current through single NMDAR cation channels and GABABR anions channels at −70 mV is inward. Extracellular and intracellular recording solutions were adjusted so that there were approximately equal concentrations of cation‐permeable ions on either side of the cell membrane (in NMDAR recordings) and approximately equal concentration of Cl ions on either side of the membrane (in GABABR recordings). Recordings were kindly provided by Dr. Sergiy Sylantyev (Institute of Neurology, UCL, UK). Artwork by Kelly L McGuire.

Figure 4.

Illustration of five major classes of ion channel structures: dimer, trimer, tetramer, pentamer and hexamer. In all but the dimer structure, one ion pore is located at the central axis formed by the association of each protein domain or subunit. In the dimer, there are two ion pores, one in each of the main domains. Within each subunit or domain 2–6 α‐helices snake back and forth across the plasma membrane creating transmembrane spanning regions (not shown). Examples of dimers include ClC Cl channels; timers include ATP‐gated P2X receptor cation channels; tetramers include all voltage‐gated ion channels, cyclic nucleotide‐gated cation channels and calcium‐activated K+; pentamers include nicotinic acetylcholine receptor cation channels, GABAB receptors anion channels and hexamers include Orai calcium‐permeable channels, and gap junction connexins. Artwork by Kelly L McGuire and Diane Lipscombe.

Figure 5.

Inside the ion pore of a K+‐selective ion channel. This diagram is based on the reported crystal structure of a KcsA K+‐selective ion channel (Doyle et al., ). The two ball‐like structures located within the narrow selectivity filter region of the pore represent two dehydrated K+ ions. The inner and outer vestibules of the pore are filled with water (1 Å=0.1 nm). Artwork by Kelly L McGuire.

Figure 6.

Illustrations of possible mechanisms for pore opening in different types of ion channels. Various models of ion channel gating have been proposed including an iris‐like channel opening and closing suggested for timeric P2X receptors (Hattori and Gouaux, ); pentameric ligand‐gated ion channels (pLGICs) are activated by agonist binding at the interface of subunits leading to widening of the ion pore (Horning and Mayer, ; Bouzat et al., ; Hilf and Dutzler, ) and a rotational gating model which has been proposed for a number of ion channels (Tombola et al., ). Artwork by Kelly L McGuire.



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Lipscombe, Diane, and Toro, Cecilia P(Oct 2013) Ion Channels. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000150.pub3]