Ion Transport across Nonexcitable Membranes


Membrane transport proteins can perform either active or passive ion transport. Active transport, in the absence or against the prevailing electrochemical gradient, can be either primary (ion pumps such as ATPases) or secondary (carriers performing cotransport or exchange). Passive transport of ions, down the electrochemical gradient, is largely mediated by ion channels. In a cell in the steady state, plasma‐membrane active and passive transport processes result in equal and opposite ion fluxes. The ion gradients generate an electrical potential difference (membrane voltage) across the cell membrane because the latter exhibits selective ionic permeability. The resting membrane potential in most cells is largely determined by the K+ equilibrium potential, with the cell being negative to the extracellular solution. Ion channels participate in numerous cell functions and their mutations can result in diseases whose manifestations depend on the organs and systems in which these proteins are expressed.

Key Concepts:

  • The difference in composition between intracellular and extracellular fluids depends on the barrier and transport functions of the plasma membrane.

  • Transport across the plasma membrane can be by solubility‐diffusion (via the lipid bilayer) or mediated (via membrane proteins). Ion transport is mediated via membrane proteins (channels, carriers or pumps).

  • The differences in ion concentrations across the plasma membrane determine the membrane potential difference (membrane voltage), according to the magnitude of the concentration gradients and the ion permeability.

  • Active transport is thermodynamically uphill (in the absence of or against the electrochemical gradient). It can be primary (pumps), for example, driven by ATP hydrolysis, or secondary (carriers), driven by the electrochemical gradient for one of the substrates.

  • Passive transport can occur by solubility‐diffusion via the lipid bilayer or be mediated by carriers or channels. In the case of ions passive transport is largely via channels.

  • The ion current through channels of one kind depends on the number of channels per cell or unit surface area, their open probability, their conductance and the electrochemical driving force.

  • Ion channels are classified by their selectivity to ions. The most important ion channels expressed on the plasma membrane of nonexcitable cells are selective for K+, Na+, Ca2+, H+, Cl, cations or anions.

  • Numerous genetic diseases of ion channels have been identified. They involve gain‐ or loss‐of‐function mutations that alter the function of one or more organs.

Keywords: cell composition; membrane potential; ion pumps; ion carriers; ion channels; active transport; passive transport; channelopathies

Figure 1.

Mechanisms of generation of ion gradients across the cell membrane. The three types of transport proteins are shown: pump (denoted by P; in this case, Na+/K+ ATPase), carrier (denoted by C; two examples: Na+, K+, 2Cl symporter and Na+/H+ antiporter) and channel (denoted by Ch; K+ and Cl channels). Primary active transport of Na+ and K+ by the Na+/K+ ATPase raises intracellular [K+] and lowers intracellular [Na+]. The resulting gradients across the membrane cause secondary active transport (Na+/H+ antiporter: downhill Na+ entry coupled to uphill H+ exit; Na+, K+, 2Cl symporter: downhill Na+ entry coupled to uphill K+ and Cl entry) and passive transport (K+ and Cl efflux across the respective channels). In the steady state, the influx and efflux for each ion are equal and thus the amounts in the cell remain constant.

Figure 2.

Sodium gradient hypothesis. Entry of organic substrate (S, e.g. glucose or amino acid) across the apical membrane of an epithelial cell (renal proximal tubule or small intestine) is via cotransport with Na+, using the Na+ electrochemical gradient. Main transporters at the basolateral membrane (uniporter for S, Na+/K+ATPase and K+ channel) are also indicated.

Figure 3.

Mutations of the CFTR can alter its function by four main mechanisms. These include alterations in protein synthesis (I), processing (II), regulation by signal transduction systems (III) or ion conduction (IV). Similar mechanisms apply to the regulation and pathology of any ion channel. Based on Welsh and Smith . ATP, adenosine triphosphate; PKA, protein kinase A; ER, endoplasmic reticulum.

Figure 4.

Schematic representation of the structure of a bacterial K+ channel (closed state). Left, only two (of the four) subunits are shown, for simplicity. The ‘selectivity filter’ (top) is lined by carbonyl groups with four sites in which dehydrated K+ ions (blue circles) fit. Towards the cell interior (bottom) the channel forms a cavity in which K+ is hydrated. Because of electrostatic repulsion between ions in the selectivity filter, positions 1 and 3 or 2 and 4 are occupied at a given time. The four sites in the selectivity filter mimic the hydration shell surrounding a potassium ion in solution (not shown). Pore helices in blue. When the channel opens, these helices separate. Right, view of the channel from the cell interior. The four subunits are depicted, as well as a K+ coordinated in the selectivity filter. Figure courtesy of Dr. LG Cuello.



Brini M and Carafoli E (2009) Calcium pumps in health and disease. Physiological Reviews 89: 1341–1378.

Butterworth MB, Edinger RS, Frizzell RA and Johnson JP (2009) Regulation of the epithelial sodium channel by membrane trafficking. American Journal of Physiology Renal Physiology 296: F10–F24.

Chadha V and Alon US (2009) Hereditary renal tubular disorders. Seminars in Nephrology 29: 399–411.

Chen TY and Hwang TC (2008) CLC‐0 and CFTR: chloride channels evolved from transporters. Physiological Reviews 88: 351–387.

DeCoursey TE (2008) Voltage‐gated proton channels. Cellular and Molecular Life Sciences 65: 2554–2573.

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

Duran C, Thompson CH, Xiao Q and Hartzell HC (2010) Chloride channels: often enigmatic, rarely predictable. Annual Review of Physiology 72: 95–121.

Dutzler R, Campbell EB, Cadene M, Chait BT and MacKinnon R (2002) X‐ray structure of a ClC chloride channel at 3.0 A reveals the molecular basis of anion selectivity. Nature 415: 287–294.

Dutzler R, Campbell EB and MacKinnon R (2003) Gating the selectivity filter in ClC chloride channels. Science 300: 108–112.

Gumz ML, Lynch IJ, Greenlee MM, Cain BD and Wingo CS (2010) The renal H+‐K+‐ATPases: physiology, regulation, and structure. American Journal of Physiology Renal Physiology 298: F12–F21.

Harris AL (2001) Emerging issues of connexin channels: biophysics fills the gap. Quarterly Reviews of Biophysics 34: 325–472.

Jentsch TJ (2008) CLC chloride channels and transporters: from genes to protein structure, pathology and physiology. Critical Reviews in Biochemistry and Molecular Biology 43: 3–36.

Latorre R, Zaelzer C and Brauchi S (2009) Structure‐functional intimacies of transient receptor potential channels. Quarterly Reviews of Biophysics 42: 201–246.

Long SB, Campbell EB and MacKinnon R (2005) Crystal structure of a mammalian voltage‐dependent Shaker family K+ channel. Science 309: 897–903.

MacKinnon R (2004) Nobel lecture: potassium channels and the atomic basis of selective ion conduction. Bioscience Reports 24: 75–100.

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

Morth JP, Pedersen BP, Toustrup‐Jensen MS et al. (2007) Crystal structure of the sodium‐potassium pump. Nature 450: 1043–1049.

Okada Y, Sato K and Numata T (2009) Pathophysiology and puzzles of the volume‐sensitive outwardly rectifying anion channel. Journal of Physiology 587: 2141–2149.

Pedersen BP, Buch‐Pedersen MJ, Morth JP, Palmgren MG and Nissen P (2007) Crystal structure of the plasma membrane proton pump. Nature 450: 1111–1114.

Planells‐Cases R and Jentsch TJ (2009) Chloride channelopathies. Biochimica et Biophysica Acta 1792: 173–189.

Remedi MS and Koster JC (2010) K(ATP) channelopathies in the pancreas. Pflűgers Archiv European Journal of Physiology 460: 307–320.

Saroussi S and Nelson N (2009) The little we know on the structure and machinery of V‐ATPase. Journal of Experimental Biology 212: 1604–1610.

Shinoda T, Ogawa H, Cornelius F and Toyoshima C (2009) Crystal structure of the sodium‐potassium pump at 2.4 A resolution. Nature 459: 446–450.

Taylor CW, Prole DL and Rahman T (2009) Ca(2+) channels on the move. Biochemistry 48: 12062–12080.

Toyoshima C (2009) How Ca2+‐ATPase pumps ions across the sarcoplasmic reticulum membrane. Biochimica et Biophysica Acta 1793: 941–946.

Toyoshima C, Nakasako M, Nomura H and Ogawa H (2000) Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 Å resolution. Nature 405: 647–655.

Welling PA and Ho K (2009) A comprehensive guide to the ROMK potassium channel: form and function in health and disease. American Journal of Physiology Renal Physiology 297: F849–F863.

Welsh MJ and Smith AE (1993) Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell 73: 1251–1254.

Further Reading

Ashcroft FM (2000) Ion Channels and Disease. San Diego: Academic Press.

Hille B (2001) Ionic Channels of Excitable Membranes, 3rd edn. Sunderland: Sinauer.

Läuger P (1991) Electrogenic Ion Pumps. Sunderland: Sinauer.

Reuss L (1997) Epithelial transport. In: Hoffman JE and Jamieson J (eds) Handbook of Physiology, section 14, Cell Physiology, pp. 309–388. New York: Oxford University Press.

Sperelakis N (2001) Cell Physiology, 3rd edn. San Diego: Academic Press.

Stein WD (1986) Transport and Diffusion Across Cell Membranes. Orlando: Academic Press.

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

* Required Field

How to Cite close
Reuss, Luis(Jan 2011) Ion Transport across Nonexcitable Membranes. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001264.pub3]