Paradoxical electromechanical effect of lanthanum ions in cardiac muscle cells

Mead, R. Hardwin; Clusin, William T.

doi:10.1016/s0006-3495(85)83827-3

Cited by 14 publications

(6 citation statements)

References 33 publications

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“…hyperpolarization was slight (control: 25-5 +I P0 mV, n = 3; with La3+: 21P8 +I P0 mV, n = 4, P < 0-025) and, curiously, it appeared to potentiate the accompanying contracture since it proved very difficult to maintain stable impalements during these experiments. This potentiation by La3+ has been directly observed by Coraboeuf et al (1981) and Mead & Clusin (1985).…”

Section: Effects Of Cs+ Ba2+ Andl Lac+ On Low-[na+]0 Hyperpolarizationssupporting

confidence: 62%

Effects of sodium‐potassium pump inhibition and low sodium on membrane potential in cultured embryonic chick heart cells.

Jacob

Lieberman

Murphy

et al. 1987

The Journal of Physiology

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SUMMARY1. When the Na+-K+ pump of cultured embryonic chick heart cells was inhibited by addition of ouabain with or without removal of external K+, the membrane potential rapidly depolarized to -40 mV and the Na+ content approximately doubled within 3 min.2. After this, exposure to an [Na+]. of 27 mm caused a fall in Na+ content, a gain in Ca2+ content and a hyperpolarization. The hyperpolarization was ' 25 mV in a [K+]. of 0 or 5-4 mm after 3 min of pump inhibition. After -10 min of pump inhibition, the same hyperpolarization was observed in a [K+]. of5-4 mm but in K+-free solution the hyperpolarization increased to -44 mV.3. Varying [K+]o during the 10 min period of Na+-K+ pump inhibition showed that the increase in hyperpolarization was associated with the period of exposure to K+-free solution rather than the [K+]. at the time of lowering [Na+]0. 4. Changes in Na+ and Ca2+ content induced by exposure to an [Na+]o of 27 mM in K+-free solution were similar at 3 and 10 min. This and the above observations suggest that the increased hyperpolarization was due to an increased membrane resistance.5. 10 mM-Cs+ reduced the low- [Na+]. hyperpolarization by 26 % but did not significantly affect the movements of Na+ and Ca2+. 1 mM-LaS+ reduced the low- [Na+]. hyperpolarization by 15 %: it also totally blocked the rise in Ca2+ content and partially blocked the fall in Na+ content. 1 mM-Ba2+ reduced the low-[Na+].hyperpolarization by 20 %. 6. Raising [Ca2+1] from 2-7 to 13-5 mm produced similar but smaller hyperpolarizations (-6 mV after 3 min pump inhibition). High [Ca2+]. caused a rise in Ca2+ content but no significant drop in Na+ content. The hyperpolarization in high [Ca2+].

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Section: Effects Of Cs+ Ba2+ Andl Lac+ On Low-[na+]0 Hyperpolarizationssupporting

confidence: 62%

Effects of sodium‐potassium pump inhibition and low sodium on membrane potential in cultured embryonic chick heart cells.

Jacob

Lieberman

Murphy

et al. 1987

The Journal of Physiology

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“…This is based on the assumption that aluminium indeed acts intracellularly, as proposed for lanthanum ions (Peeters et al, 1989). Interestingly, secondary positive inotropic effects of lanthanum were also abolished by caffeine (Mead & Clusin, 1985).…”

Section: Transmembrane Ionic Currentsmentioning

confidence: 99%

“…The most likely effect of exposure to aluminium is an increase in the release of calcium from intracellular stores. Some displacement may occur from sarcolemmal binding sites (Langer, 1984), as proposed for the action of lanthanum (Mead & Clusin, 1985). Any massive 'dumping' of calcium, however, would have led to increases in baseline, tonic tension.…”

Section: Transmembrane Ionic Currentsmentioning

confidence: 99%

Effects of aluminium on electrical and mechanical properties of frog atrial muscle

Meiri

Shimoni

1991

British J Pharmacology

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The effects of aluminium on membrane ionic currents were studied in single cardiac myocytes. Most of the work was done on frog atrial cells, but some experiments were also carried out on single cells isolated from rabbit ventricles and atria. The effects of aluminium on the force of contraction of frog atrial trabeculae were also investigated. Aluminium was prepared from AlCl3 as a stock 0.5 m solution which has a pH of 3.5. Before each experiment, this solution was added to the control solution, to give a final concentration of 20–100 μg ml−1 aluminium (0.75–3.75 mm AlCl3). The solutions were brought to a pH of 7.4 or 7.6, at which they consist of a mixture of amorphous aluminium hydroxides and a very small amount of soluble ionic aluminium complexes: free aluminium cations (less than 10 pm), aluminohydroxide anions (less than 8 μm). The addition of this suspension reduced the peak inward calcium currents in single rabbit atrial and ventricular cells and in frog atrial cells. In the latter, the peak current was reduced (at + 10 mV) to 45% of control (mean of 9 cells). This effect was reversible upon washout, and was obtained at all membrane potentials, with no shift of the calcium current voltage relationship along the voltage axis. Aluminium also reduced the time‐dependent potassium current IK. This reduction was observed at all membrane potentials. For example, at + 10 mV, the mean reduction of IK (n = 9) was to 69% of the control amplitude. This effect, which was very difficult to reverse, was not due to IK rundown. The fully activated current‐voltage relationships (obtained by standard ‘tail’ analysis) showed that the effect of aluminium was due mainly to a decrease in conductance and not to a shift in the activation range of IK. The mean voltage of half activation was shifted by 8 mV in the depolarizing direction (n = 5). The background potassium current IK1 was also slightly but consistently changed in a complex fashion, with an outward shift at membrane potentials positive to −60 mV. For example, at a membrane potential of −40 mV, the mean shift was by 22 ± 4 pA. At more negative potentials, there was an inward shift in the current amplitudes. For example, for steps to −100 mV the current elicited was larger (more inward) by 53 pA (mean value, n = 10). The reversal potential was slightly shifted (< 10 mV) in the hyperpolarizing direction. The force of contraction of frog atrial trabeculae was altered by aluminium in a complex manner, which showed marked seasonal variation. During most of the year, 50–100 μg ml−1 aluminium caused a biphasic change, with an early small and consistent decrease, followed by a large increase in twitch amplitude. For a short period corresponding to the (local) winter months the sensitivity to aluminium was greatly enhanced. Aluminium 100 μg ml−1 totally abolished contraction (n = 5), while a lower concentration (20 μg ml−1) produced a sustained reduction in the force of contraction. Similar biphasic and seasonal responses have been reported to be induced by lanthanum. The biph...

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“…La3" has been widely used as a probe of Ca2"-activated/ mediated biological processes because of its ability to replace Ca2" at binding sites (Lettvin et al, 1964;Takata et al, 1966;van Breemen and de Weer, 1970;Heuser and Miledi, 1971;Weiss, 1974;Smith, 1976;Evans, 1983;Mead and Clusin, 1985;Curtis et al, 1986;Segal, 1986). The physicochemical basis of this observation was proposed by Lettvin et al (1964) based upon the similar ionic radii of these cations.…”

Section: Introductionmentioning

confidence: 99%

La3+-induced fusion of phosphatidylserine liposomes. Close approach, intermembrane intermediates, and the electrostatic surface potential

Bentz¹,

Alford²,

Cohen³

et al. 1988

Biophysical Journal

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The fusion of large unilamellar phosphatidylserine liposomes (PS LUV) induced by La3+ has been monitored using the 1-aminoapthalene-3,6,8-trisulfonic acid/p-xylenebis(pyridinium bromide) (ANTS/DPX) fluorescence assay for the mixing of aqueous contents. The fusion event is extensive and nonleaky, with up to 95% mixing of contents in the fused liposomes. However, addition of excess EDTA leads to disruption of the fusion products in a way that implies the existence of metastable intermembrane contact sites. The maximal fusion activity occurs between 10 and 100 microM La3+ and fusion can be terminated rapidly, without loss of contents, by the addition of excess La3+, e.g., 1 mM La3+ at pH 7.4. This observation is explained by the very large intrinsic binding constant (approximately 10(5) M-1) of La3+ to the PS headgroup, as measured by microelectrophoresis. Addition of 1 mM La3+ causes charge reversal of the membrane and a large positive surface potential. La3+ binding to PS causes the release of a proton. These data can be explained if La3+ can chelate to PS at two sites, with one of the sites being the primary amino group. This binding model successfully predicts that at pH 4.5 fusion occurs up to 2 mM La3+, due to reduced La3+ binding at low pH. We conclude that the general mechanism of membrane fusion includes three kinetic steps. In addition to (a) aggregation, there is (b) the close approach of the surfaces, or thinning of the hydration layer, and (c) the formation of intermembrane intermediates which determine the extent to which membrane destabilization leads to fusion (mixing of aqueous contents), as opposed to lysis. The lifetime of these intermembrane intermediates appears to depend upon La3+ binding to both PS sites.

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Paradoxical electromechanical effect of lanthanum ions in cardiac muscle cells

Cited by 14 publications

References 33 publications

Effects of sodium‐potassium pump inhibition and low sodium on membrane potential in cultured embryonic chick heart cells.

Effects of sodium‐potassium pump inhibition and low sodium on membrane potential in cultured embryonic chick heart cells.

Effects of aluminium on electrical and mechanical properties of frog atrial muscle

La3+-induced fusion of phosphatidylserine liposomes. Close approach, intermembrane intermediates, and the electrostatic surface potential

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