Sodium-Calcium Exchange Activity Generates a Current in Cardiac Membrane Vesicles

Reeves, John P.; Sutko, John L.

doi:10.1126/science.7384788

Cited by 176 publications

(47 citation statements)

References 30 publications

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“…In heart sarcolemmal preparations, the Na+/Ca2 + system operates electrogenically, exchanging three or more Na + ions for one Ca2 + (Pitts, 1979;Reeves & Sutko, 1980;Philipson & Nishimoto, 1980). It has therefore been suggested that in heart Na+/Ca2 + exchange could contribute not only to Ca2 + extrusion during relaxation but also to Ca2 + entry during depolarization.…”

Section: Discussionmentioning

confidence: 99%

Sodium/calcium exchange in smooth-muscle microsomal fractions

Morel¹,

Godfraind²

1984

Biochemical Journal

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1. The existence of Na+-dependent Ca2 + transport was investigated in microsomal fractions from the longitudinal smooth muscle of the guinea-pig ileum and from the rat aorta, and its activity was compared with that of the plasmalemmal ATPdependent Ca2+ pump previously identified in these preparations. 2. The rate of Ca2 + release from plasmalemmal vesicles previously loaded with Ca2 + through the ATP-dependent Ca2 + pump was transiently faster in the presence of 150 mM-NaCl in the medium than in the presence of 150mM-KCl or -LiCl or 300mM-sucrose. 3. Na+-loaded vesicles took up Ca2 + when an outwardly directed Na+ gradient was formed across the membrane. The Ca ionophore A23 187 induced a rapid release of 85% of the sequestered Ca2 +, whereas only 15% was displaced by La3 +. Ca2 + accumulated by the Na + -induced Ca2 + transport was released by the addition of NaCl, but not KCI, to the medium. 4. Ca2 + uptake in Na+-loaded vesicles was inhibited in the presence of increasing NaCl concentration in the medium. Half-maximum inhibition was observed with 28 mM-NaCl. Data fitted the Hill equation, with a Hill coefficient (h) of 1.9. 5. Na +-induced Ca2 + uptake was a saturable function of Ca2 + concentration in the medium. Half-maximum activity was obtained with 18 M-Ca2+ in intestinalsmooth-muscle microsomal fraction and with 50,uM-Ca2 + in aortic microsomal fraction. 6. The results suggest that in these membrane preparations a transmembrane movement of Ca2+ can be driven by a Nal gradient. However, the Na+-induced Ca2 + transport had a lower capacity, a lower affinity and a slower rate than the ATP-dependent Ca2 + pump.

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Section: Discussionmentioning

confidence: 99%

Sodium/calcium exchange in smooth-muscle microsomal fractions

Morel¹,

Godfraind²

1984

Biochemical Journal

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“…Although an Na/Ca exchange has been implicated in heart as a primary mechanism for the regulation of [Ca]; (Reuter and Seitz, 1968;Jundt et al, 1975), until recently it was not possible to decide whether such a mechanism was electrogenic or electroneutral . Convincing evidence recently obtained from flux studies in isolated cardiac sarcolemmal vesicles indicates that more than two Na ions are transported for each Ca and that the exchanger is voltage dependent (Pitts, 1979 ;Bers et al ., 1980 ;Caroni et al ., 1980;Reeves and Sutko, 1980) . Studies using measurements of intracellular ion activities also have provided evidence that the Na/Ca exchange mechanism in the heart is electrogenic (Bers and Ellis, 1982;Sheu and Fozzard, 1982 ;Chapman et al, 1983a ;Eisner et al ., 1983).…”

Section: Discussionmentioning

confidence: 99%

"Creep currents" in single frog atrial cells may be generated by electrogenic Na/Ca exchange.

Hume¹,

Uehara²

1986

The Journal of General Physiology

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The objective of these experiments was to test the hypothesis that the "creep currents" induced by Na loading of single frog atrial cells (Hume, J . R ., and A . Uehara . 1986 . Journal of General Physiology. 87 :833) may be generated by an electrogenic Na/Ca exchanger . Creep currents induced by Na loading were examined over a wide range of membrane potentials . During depolarizing voltage-clamp pulses, outward creep currents were observed, followed by inward creep currents upon the return to the holding potential .During hyperpolarizing voltage-clamp pulses, creep currents of the opposite polarity were observed : inward creep currents were observed during the pulses, followed by outward creep currents upon the return to the holding potential . The current-voltage relations for inward and outward creep currents in response to depolarizing or hyperpolarizing voltage displacements away from the holding potential all intersect the voltage axis at a common potential, which indicates that inward and outward creep currents may have a common reversal potential under equilibrium conditions and may therefore be generated by a common mechanism . Measurements of inward creep currents confirm that voltage displacements away from the holding potential rapidly alter equilibrium conditions . Current-voltage relationships of inward creep currents after depo-

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“…Na-Ca exchange in other systems has been reported to be electrogenic, that is more than two Na ions are exchanged for each Ca2+ (Baker & McNaughton, 1976;Blaustein, 1977;Pitts, 1979;Reeves & Sutko, 1980;Philipson & Nishimoto, 1980). Therefore, the effect of different ionophores on the rate and amount of Na-Ca exchange was investigated (Fig.…”

Section: Preparationsmentioning

confidence: 99%

Sodium‐calcium exchange in the outer segments of bovine rod photoreceptors.

Schnetkamp¹

1986

The Journal of Physiology

100

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SUMMARY1. Intact rod outer segments (r.o.s.) isolated from bovine retinas were used to measure net Ca2+ fluxes using the optical Ca2+ indicator Arsenazo III. Ca2+ fluxes were observed, which could change the internal Ca2+ content of isolated r.o.s. by as much as 0 5 mM s-5.2. The Ca2+ content of isolated intact r.o.s. was strongly dependent on the Na/Ca ratio in the isolation medium, and could be made less than 01 mol Ca2+ mold1 rhodopsin (zero Ca2+ in isolation medium) or up to 7 mol Ca2+ mold1 rhodopsin (zero Na+ in isolation medium).3. Ca2+ efflux from r.o.s. rich in Ca2+ was observed only when Na+ was added to the external medium (as opposed to any other alkali cation); in Ca2+-depleted r.o.s. Ca2+ uptake required the presence of internal Na+ and was inhibited selectively by external Na+. These results suggest that Na-Ca exchange across the plasma membrane operated freely in both directions and controlled the internal Ca2+ concentration in r.o.s.4. Na+-stimulated Ca2+ efflux depended on the external Na+ concentration in a sigmoidal way. This suggests that the simultaneous binding of two Na ions is rate limiting for transport.5. In Ca2+-depleted r.o.s. and in the absence of external Na+, 1 mol Ca2+ mold1 rhodopsin (or 3 mM-total Ca2+) could be taken up within 1 min by intact r.o.s. at a free external Ca2+ concentration of about 1 /tM. 6. Only part of the internal Ca2+ was available for Na-Ca exchange. The external Na+ and K+ concentration as well as the temperature were factors controlling the accessibility of internal Ca2+ to participate in Na-Ca exchange.7. Ca2+ fluxes in r.o.s. with a permeabilized plasma membrane but intact disk membranes were very similar to those observed in intact r.o.s.; Na-Ca exchange could operate in both directions across the disk membrane.8. In addition to Na-Ca exchange, leaky r.o.s. also showed a guanosine 3', 5'-cyclic monophosphate (cyclic GMP)-induced Ca2+ release that was about I of the rate of Present address:

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Sodium-Calcium Exchange Activity Generates a Current in Cardiac Membrane Vesicles

Cited by 176 publications

References 30 publications

Sodium/calcium exchange in smooth-muscle microsomal fractions

Sodium/calcium exchange in smooth-muscle microsomal fractions

"Creep currents" in single frog atrial cells may be generated by electrogenic Na/Ca exchange.

Sodium‐calcium exchange in the outer segments of bovine rod photoreceptors.

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