Electrogenic Na+/Ca2+-exchange of nerve and muscle cells.
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.
Török
Tamás L
TL
Department of Pharmacodynamics, Semmelweis University, P.O. Box 370, VIII. Nagyvárad-tér 4, H-1445 Budapest, Hungary. tortam@net.sote.hu
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
D019831:Sodium-Calcium Exchanger; D002118:Calcium