Charge movement during Na+ translocation by native and cloned cardiac Na+/Ca2+ exchanger

Donald W. Hilgemann, Debora A. Nicoll, Kenneth D. Philipson

Research output: Contribution to journalArticle

166 Citations (Scopus)

Abstract

Na+/Ca2+ EXCHANGE is electrogenic and moves one net positive charge per cycle1,2. Although the cardiac exchanger has a three-to-one Na+/Ca2+ stoichiometry3, details of the reaction cycle are not well defined2,4-8. Here we associate Na+ translocation by the cardiac exchanger with positive charge movement in giant membrane patches from cardiac myocytes9,10 and oocytes expressing the cloned cardiac Na+/Ca2+ exchanger11. The charge movements are initiated by step increments of the cytoplasmic Na+ concentration in the absence of Ca2+. Giant patches from control oocytes lack both steady-state Na+/Ca2+ exchange current (INaCa) and Na+-induced charge movements. Charge movements indicate about 400 exchangers per μm2 in guinea-pig sarcolemma. Fully activated INaCa densities (20-30 μA cm-2) indicate maximum turnover rates of 5,000 s-1. As has been predicted for consecutive exchange models4-7, the apparent ion affinities of steady state INaCa increase as the counterion concentrations are decreased. Consistent with an electroneutral Ca2+ translocation, we find that voltage dependence of INaCa in both directions is lost as Ca2+ concentration is decreased. The principal electrogenic step seems to be at the extracellular end of the Na+ translocation pathway.

Original languageEnglish (US)
Pages (from-to)715-718
Number of pages4
JournalNature
Volume352
Issue number6337
StatePublished - Aug 22 1991

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Oocytes
Sarcolemma
Guinea Pigs
Ions
Membranes
Direction compound

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Cite this

Charge movement during Na+ translocation by native and cloned cardiac Na+/Ca2+ exchanger. / Hilgemann, Donald W.; Nicoll, Debora A.; Philipson, Kenneth D.

In: Nature, Vol. 352, No. 6337, 22.08.1991, p. 715-718.

Research output: Contribution to journalArticle

Hilgemann, DW, Nicoll, DA & Philipson, KD 1991, 'Charge movement during Na+ translocation by native and cloned cardiac Na+/Ca2+ exchanger', Nature, vol. 352, no. 6337, pp. 715-718.
Hilgemann, Donald W. ; Nicoll, Debora A. ; Philipson, Kenneth D. / Charge movement during Na+ translocation by native and cloned cardiac Na+/Ca2+ exchanger. In: Nature. 1991 ; Vol. 352, No. 6337. pp. 715-718.
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AB - Na+/Ca2+ EXCHANGE is electrogenic and moves one net positive charge per cycle1,2. Although the cardiac exchanger has a three-to-one Na+/Ca2+ stoichiometry3, details of the reaction cycle are not well defined2,4-8. Here we associate Na+ translocation by the cardiac exchanger with positive charge movement in giant membrane patches from cardiac myocytes9,10 and oocytes expressing the cloned cardiac Na+/Ca2+ exchanger11. The charge movements are initiated by step increments of the cytoplasmic Na+ concentration in the absence of Ca2+. Giant patches from control oocytes lack both steady-state Na+/Ca2+ exchange current (INaCa) and Na+-induced charge movements. Charge movements indicate about 400 exchangers per μm2 in guinea-pig sarcolemma. Fully activated INaCa densities (20-30 μA cm-2) indicate maximum turnover rates of 5,000 s-1. As has been predicted for consecutive exchange models4-7, the apparent ion affinities of steady state INaCa increase as the counterion concentrations are decreased. Consistent with an electroneutral Ca2+ translocation, we find that voltage dependence of INaCa in both directions is lost as Ca2+ concentration is decreased. The principal electrogenic step seems to be at the extracellular end of the Na+ translocation pathway.

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