Electrogenic Na+/Ca2+-exchange of nerve and muscle cells

Prog Neurobiol. 2007 Aug;82(6):287-347. doi: 10.1016/j.pneurobio.2007.06.003. Epub 2007 Jun 21.


The plasma membrane Na(+)/Ca(2+)-exchanger is a bi-directional electrogenic (3Na(+):1Ca(2+)) and voltage-sensitive ion transport mechanism, which is mainly responsible for Ca(2+)-extrusion. The Na(+)-gradient, required for normal mode operation, is created by the Na(+)-pump, which is also electrogenic (3Na(+):2K(+)) and voltage-sensitive. The Na(+)/Ca(2+)-exchanger operational modes are very similar to those of the Na(+)-pump, except that the uncoupled flux (Na(+)-influx or -efflux?) is missing. The reversal potential of the exchanger is around -40 mV; therefore, during the upstroke of the AP it is probably transiently activated, leading to Ca(2+)-influx. The Na(+)/Ca(2+)-exchange is regulated by transported and non-transported external and internal cations, and shows ATP(i)-, pH- and temperature-dependence. The main problem in determining the role of Na(+)/Ca(2+)-exchange in excitation-secretion/contraction coupling is the lack of specific (mode-selective) blockers. During recent years, evidence has been accumulated for co-localisation of the Na(+)-pump, and the Na(+)/Ca(2+)-exchanger and their possible functional interaction in the "restricted" or "fuzzy space." In cardiac failure, the Na(+)-pump is down-regulated, while the exchanger is up-regulated. If the exchanger is working in normal mode (Ca(2+)-extrusion) during most of the cardiac cycle, upregulation of the exchanger may result in SR Ca(2+)-store depletion and further impairment in contractility. If so, a normal mode selective Na(+)/Ca(2+)-exchange inhibitor would be useful therapy for decompensation, and unlike CGs would not increase internal Na(+). In peripheral sympathetic nerves, pre-synaptic alpha(2)-receptors may regulate not only the VSCCs but possibly the reverse Na(+)/Ca(2+)-exchange as well.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Signaling / physiology*
  • Humans
  • Membrane Potentials / physiology*
  • Muscle Fibers, Skeletal / physiology*
  • Neurons / physiology*
  • Sodium-Calcium Exchanger / metabolism*
  • Synaptic Transmission / physiology*


  • Sodium-Calcium Exchanger
  • Calcium