Sodium, Calcium and Potassium Channels

Abstract

Sodium, calcium and potassium channels form the basis for the electrical excitability of various cell types. They are membrane proteins which harbour voltage‐gated pores providing selective permeation pathways for Na+, Ca2+ and K+ ions, respectively.

Keywords: voltage‐dependent gating; ion selectivity; gene family; excitability; ion current

Figure 2.

Functional and structural properties of voltage‐gated sodium and calcium channels. (a) Subunit composition of voltage‐gated sodium and calcium channels. (b) Putative organization of the α subunit of sodium channels in the membrane. The boxes indicate protein segments that are highly likely to span the membrane. The S4 segment (red) contains a high density of positively charged residues and serves as a voltage sensor. The green loop (P‐region) is the major determinant for the ion permeation pathway. The IFM motif (amino acids Ile‐Phe‐Met) in the cytosolic linker between repeats III and IV is important for the rapid channel inactivation. (c) Voltage‐clamp current recordings from mammalian host cells transfected with the µI sodium channel gene from rat skeletal muscle. The current traces are responses to the indicated steps in membrane potential. (d) Peak current versus test voltage from the experiment shown in (c). Note the activation threshold of sodium channels at around −40 mV and the reversal potential for Na+ ions close to +50 mV (arrows).

Figure 1.

Functional and structural properties of voltage‐gated and inward rectifying potassium channels. (a) Subunit composition of voltage‐gated (Kv) and inward rectifying (Kir) potassium channels. The channel‐forming pores are composed of four α subunits (grey). α Subunits of Kv channels have a voltage‐sensing S4 transmembrane segment that undergoes conformation changes upon changes in the transmembrane electric field inducing closed (left) and open (right) states of the channel pore. Some species of Kv channels associate with cytosolic β subunits (left). (b) Putative organization of the α subunits of potassium channels in the membrane. Kir channels lack segments S1–S4. (c) Voltage‐clamp current recordings from Xenopus laevis oocytes that were injected with mRNA coding for the delayed rectifier channel hKv1.5 (black) and the transient A type potassium channel rKv1.4 (red). (d) The peak currents of the experiments shown in (c) are plotted as a function of test voltage (circles). Also included in this current–voltage plot is a current trace recorded from oocytes expressing the inward rectifier channel mKir2.1 (green). The black and red arrows indicate the activation thresholds for the Kv channels; the green arrow indicates the reversal potential for K channels.

Figure 3.

Overview of the gene family of potassium channel‐forming protein subunits and related proteins, showing the most important members only (modified after Wei et al., ). Based on potassium channels with 2 and 6 transmembrane segments (2TM and 6TM), further channel‐forming proteins have presumably evolved by gene duplication and splicing: 2∗2TM (TWIK channels), 6+2TM (TOK channels), and 4∗6TM (sodium and calcium channels). Several members of the 2TM and 6TM families are indicated. Owing to the rapid progress in the cloning of channel genes, there are many more members expected to be isolated, as indicated by dots.

close

References

Doyle DA, Cabral JM, Pfuetzner RA et al. (1998) The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280: 69–77.

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

Heinemann SH, Terlau H, Stühmer W, Imoto K and Numa S (1992) Calcium channel characteristics conferred on the sodium channel by single mutations. Nature 356: 441–443.

Hodgkin AL and Huxley AF (1952) A quantitative description of membrane current and its application to conduction and excitation in nerve. Journal of Physiology (London) 117: 500–544.

Hoshi T, Zagotta WN and Aldrich RW (1990) Biophysical and molecular mechanisms of Shaker potassium channel inactivation. Science 250: 533–538.

Kubo Y, Baldwin TJ, Jan YN and Jan LY (1993) Primary structure and functional expression of a mouse inward rectifier potassium channel. Nature 362: 127–133.

Rettig J, Heinemann SH, Wunder F et al. (1994) Inactivation properties of voltage‐gated K+ channels altered by presence of β‐subunit. Nature 369: 289–294.

Stühmer W, Conti F, Suzuki H et al. (1989) Structural parts involved in activation and inactivation of the sodium channel. Nature 339: 597–603.

Wei A, Jegla T and Salkoff L (1996) Eight potassium channel families revealed by the C. elegans genome project. Neuropharmacology 35: 805–829.

West JW, Patton DE, Scheuer T et al. (1992) A cluster of hydrophobic amino acid residues required for fast Na+‐channel inactivation. Proceedings of the National Academy of Sciences of the USA 89: 10910–10914.

Further Reading

Aidley DJ and Stanfield PR (1996) Ion Channels. Molecules in Action. Cambridge: Cambridge University Press.

Armstrong CM and Hille B (1998) Voltage‐gated ion channels and electrical excitability. Neuron 20: 371–380.

Biel M, Zong X and Hofmann F (1996) Cyclic nucleotide‐gated cation channels. Molecular diversity, structure, and cellular functions. Trends in Cardiovascular Medicine 6: 274–280.

Chandy KG and Gutman GA (1995) Voltage gated K+ channel genes. In: North RA (ed.) Handbook of Receptors and Channels, pp. 1–71. Boca Raton, FL: CRC Press.

Dascal N (1997) Signaling via the G‐protein‐activated K+ channels. Cellular Signalling 9: 551–573.

Hebert SC (1998) General principles of the structure of ion channels. American Journal of Medicine 104: 87–98.

Hille B (1992) Ionic Channels of Excitable Membranes, 2nd edn. Sunderland, MA: Sinauer Associates.

Isom LL, DeJongh KS and Catterall WA (1994) Auxiliary subunits of voltage‐gated ion channels. Neuron 12: 1183–1194.

Jan LY and Jan YN (1997) Cloned potassium channels from eukaryotes and prokaryotes. Annual Review of Neuroscience 20: 91–123.

Marban E, Yamagishi T and Tomaselli GF (1998) Structure and function of voltage‐gated sodium channels. Journal of Physiology 508: 647–657.

Randall AD (1998) The molecular basis of voltage‐gated Ca2+ channel diversity: is it time for T? Journal of Membrane Biology 161: 207–213.

Vergara C, Latorre R, Marrion NV and Adelman JP (1998) Calcium‐activated potassium channels. Current Opinion in Neurobiology 8: 321–329.

Walker D and De Waard M (1998) Subunit interaction sites in voltage‐gated Ca2+ channels: role in channel function. Trends in Neurosciences 21: 148–154.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Heinemann, Stefan H(Apr 2001) Sodium, Calcium and Potassium Channels. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0000653]