Transmembrane Na+ and Ca2+ electrochemical gradients in cardiac muscle and their relationship to force development.

Sheu, S S; Fozzard, Harry A.

doi:10.1085/jgp.80.3.325

Cited by 343 publications

(190 citation statements)

References 36 publications

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“…Ouabain has been thought to increase the contraction through a Na+-Ca2+ exchange mechanism (Reuter & Seitz, 1968;Sheu & Fozzard, 1982;Wasserstrom et al, 1983;Eisner et al, 1984;Vassalle & Lee, 1984;Wier & Hess, 1984;Grupp et al, 1985). Ouabain inhibits Na'-K' ATPase and results in an accumulation of [NaJ]i.…”

Section: Discussionmentioning

confidence: 99%

Negative inotropic effects of disopyramide on guinea‐pig papillary muscles

Kondo

Mizukami

Shibata

1990

British J Pharmacology

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The inhibitory effects of disopyramide on electromechanical responses were investigated in guinea‐pig papillary muscles driven by electrical stimuli. Disopyramide up to 10−5 m did not cause a negative inotropic effect, while the maximum upstroke velocity of the action potential (dV/dtmax) was significantly decreased. At higher concentrations, this drug dose‐dependently inhibited the contraction, and dV/dtmax was further decreased. This inhibition of contraction was accompanied by a depression of the slow action potential in partially depolarized preparations by increasing [K+]o (26 mm). In preparations pretreated with nifedipine (10−6 m) and ryanodine (10−6 m), the contraction was almost completely inhibited. In such preparations, ouabain (2 × 10−6 m) markedly increased the contraction, probably through the Na+‐Ca2+ exchange mechanism. This contraction was inhibited by disopyramide above 10−8 m, and an almost complete inhibition was caused at 3 × 10−5 m. A similar inhibitory effect was observed on the contraction increased by the lowering of [Na+]o (36 mm). These results suggest that disopyramide at high concentrations inhibits Ca influx through slow Ca2+ channels and at low concentrations, it reduces the contraction increased through the Na+‐Ca2+ exchange mechanism. Disopyramide had a greater effect on cardiac contractility mediated by the Na+‐Ca2+ exchange mechanism.

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Section: Discussionmentioning

confidence: 99%

Negative inotropic effects of disopyramide on guinea‐pig papillary muscles

Kondo

Mizukami

Shibata

1990

British J Pharmacology

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“…The counter-transport process is powered by the energy derived from the transmembrane sodium electrochemical gradient. Alterations in the gradient, either by reduction in the extracellular sodium content or by increasing the intracellular sodium via inhibition of the sodiumpotassium pump, have produced an increase in intracellular calcium, likely via this mechanism (Horackova & Vassort, 1979;Marban, Rink, Tsien & Tsien, 1980; Lee, Uhm & Dresdner, 1980b;Sheu & Fozzard, 1982;Chapman, Coray & McGuigan, 15 PHY 388 1983). It is clear, however, that the sodium-calcium exchanger is modulated by factors other than the sodium gradient per se, including membrane potential, pH and temperature (Reuter & Seitz, 1968;Deitmer & Ellis, 1980; Busselen, 1982;Phillipson, Bersohn & Nishimuta, 1982;Eisner & Lederer, 1985).…”

Section: Introductionmentioning

confidence: 99%

Intracellular sodium‐calcium dissociation in early contractile failure in hypoxic ferret papillary muscles.

Guarnieri

1987

The Journal of Physiology

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SUMMARY1. Intracellular sodium activity (aNa) and intracellular calcium activity (aca) were measured in isolated quiescent right-ventricular ferret muscle: aa = 9-8 + 22 mm and aia= 71 + 19 nm.2. When the muscles were exposed to 10-M-ouabain, aia increased to 20'4 + 3-1 mm while aia increased to 260 + 99 nm. Twitch tension approximately doubled.3. During prolonged hypoxia with glucose in the perfusate, aka and twitch tension were unchanged.4, During prolonged hypoxia with sucrose (substrate free) in the perfusate aNa increased to 18-9 + 3-1 mm, but aia did not change. Twitch tension declined by 50%.5. The addition of 10-5 M-ouabain to the substrate-free hypoxic perfusate caused aka to increase to 31-6 + 2-8 mm and aia to increase to 150 + 35 nm. Twitch tension was unchanged.6. These data indicate that only during prolonged substrate-free hypoxia does a'a increase. Despite the increase in aka, no change in aa is seen, unless the sodium-potassium pump is concomitantly inhibited. The lack of rise of aia is consistent with inhibition of the sodium-calcium exchange, although other avenues of calcium exchange cannot be excluded.

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“…The stoichiometry of the NaCa exchanger can be estimated from the ratio of electrochemical gradients for Na and Ca (Sheu and Fozzard, 1982) if it is assumed that the Na-Ca exchange is at equilibrium . However, parallel pathways for Ca movement, such as a passive Ca leak or a Ca pump-mediated Ca flux, may displace the Na-Ca exchange process from equilibrium, causing an error in the measurement of the stoichiometry from electrochemical gradient ratios (Sheu and Fozzard, 1982 ;Axelson and Bridge, 1985). The estimation of the stoichiometry from ion movements (Pitts, 1979 ;Wakabayashi and Goshima, 1981 ;Bridge and Bassingthwaighte, 1983 ;Reeves and Hale, 1984) will also be distorted by the presence of parallel pathways for Ca movement .…”

Section: Introductionmentioning

confidence: 99%

External Na-independent Ca extrusion in cultured ventricular cells. Magnitude and functional significance.

Barry

Rasmussen

Ishida

et al. 1986

The Journal of General Physiology

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The relative magnitudes and functional significance of Ca extrusion by Na-Ca exchange and by an Na.-independent mechanism were investigated in monolayer cultures of chick embryo ventricular cells. Abrupt exposure of cells in 0-Na., nominally 0-Ca. solution to 20 mM caffeine produced a large contracture (3 .94 ± 0.90 um of cell shortening) that relaxed with a tl, of 8.60 ± 1 .22 s. An abrupt exposure to caffeine plus 140 mM Na resulted in a contracture that was smaller in amplitude (1 .53 ± 0.50,um) and relaxed much more rapidly (t,, = 0.77 ± 0 .09 s) . An abrupt exposure to caffeine in 0-Na. solutions produced an increase in "Ca efflux that persisted for 20 s, and a net loss of Ca content, determined by atomic absorption spectroscopy (AAS), of^-4 nmol/mg protein, within 35 s. A comparable net loss of Ca was demonstrated in the presence of 100 jM [Ca]o. The abrupt exposure of cultured cells to 0 Na. in 1 .8 mM Ca produced a Ca uptake, estimated with 45 Ca, of 3.2 nmol/mg protein -15 s, but produced no increase in cell Ca content (AAS). In cells in which a 30% increase in Nai was produced by 5 min exposure to 10 -6 M ouabain, the abrupt exposure to 0 Na. produced a Ca uptake of 6 nmol/mg protein -15 s and an increase in Ca content (AAS) of 4 nmol/mg protein. We conclude that there is an Na.-independent mechanism for Ca extrusion in these cells, presumably a Ca-ATPase Ca pump, with a limited Ca transport capacity of no more than 2 nmol/mg protein -15 s. This is five times smaller than the demonstrated maximum capacity of the Na-Ca exchanger in these cells. The relaxation of twitch tension in these cells seems to be dependent primarily on sarcoplasmic reticulum uptake of Ca, with a secondary role provided by the Na-Ca exchanger. The Ca pump appears to contribute little to beat-to-beat relaxation .

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Transmembrane Na+ and Ca2+ electrochemical gradients in cardiac muscle and their relationship to force development.

Cited by 343 publications

References 36 publications

Negative inotropic effects of disopyramide on guinea‐pig papillary muscles

Negative inotropic effects of disopyramide on guinea‐pig papillary muscles

Intracellular sodium‐calcium dissociation in early contractile failure in hypoxic ferret papillary muscles.

External Na-independent Ca extrusion in cultured ventricular cells. Magnitude and functional significance.

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