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Journal ArticleDOI

Specific Uncoupling of Excitation and Contraction in Mammalian Cardiac Tissue by Lanthanum Kinetic studies

01 Aug 1970-The Journal of General Physiology (The Rockefeller University Press)-Vol. 56, Iss: 2, pp 191-217
TL;DR: Analysis of the quantities of 45Ca released following exposure to 10 µM La indicated that this La-susceptible Ca was being displaced from a homogeneous pool—the one previously shown by Langer to represent contractile dependent Ca.
Abstract: Arterially cannulated rabbit interventricular septal tissue was exposed to 5–40 µM La in 2.5 mM Ca perfusate. Immediately following perfusion with La two concurrent events were consistently observed: (a) a rapid decline of active tension to a lesser steady-state value, and (b) an abrupt, release of short duration of tissue-bound Ca. The magnitude of both events was directly related to the [La]o. If the duration of exposure to La was brief, contractility returned toward normal upon return to the La-free perfusate. Elevation of [Ca]o during exposure to La counteracted its effect and induced a concurrent displacement of tissue-bound La. Cellular action potentials recorded during brief perfusion with La demonstrated that essentially normal regenerative depolarization was maintained. Analysis of the quantities of 45Ca released following exposure to 10 µM La indicated that this La-susceptible Ca was being displaced from a homogeneous pool—the one previously shown by Langer to represent contractile dependent Ca. These data led to the following conclusions: During perfusion with 2.5 mM Ca contractile dependent Ca was derived primarily from "superficially" located sites. La effected the release of contractile dependent Ca by modifying the normal permselectivity of this "superficial" membrane for activator Ca. These and other data infer that contractile dependent Ca is derived primarily from superficially located sites.
Citations
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Journal ArticleDOI
TL;DR: In this article, it is suggested that although Ca2+ undertakes a primarily structural role in the Ln3+ non-inhibited proteins, Ca2+) may be near the active site or participate in the mechanism of action of Ln 3+ inhibited proteins.
Abstract: Calcium ion plays an essential role in many biological processes. The environment about Ca2+ may be probed by substitution of tripositive lanthanide ions, Ln3+. Ca2+ proteins fall into two broad classes: those that are inhibited by Ln3+ substitution and those that are not. It is suggested that although Ca2+ undertakes a primarily structural role in the Ln3+ non-inhibited proteins, Ca2+ may be near the active site or participate in the mechanism of action of Ln3+ inhibited proteins. Ca2+ and Ln3+ radii are similar; most Ln3+ are slightly larger than Ca2+ in complexes of the same coordination number, and substitution of Ln3+ for Ca2+ is accommodated by a slight decrease in bond distance or by an increase in coordination number. Luminescence from Tb3+ has been demonstrated to be a sensitive environmental probe of Ca2+ binding sites in proteins.

348 citations

Journal ArticleDOI
TL;DR: The surface of Neonatal rat cells in culture, neonatal rat hearts, and adult rabbit hearts have qualitatively similar responses to lanthanum, ruthenium red, and colloidal iron stains, indicating that the integrity of surface coat is critical in the regulation of Ca (and La) exchange but that K* permeability is controlled at the bilayer region.
Abstract: The surface of neonatal rat cells in culture, neonatal rat hearts, and adult rabbit hearts have qualitatively similar responses to lanthanum, ruthenium red, and colloidal iron stains. All demonstrate a surface coat and external lamina with abundant negatively charged sites. Cells with intact surface structure do not permit entry of lanthanum (La) intracellularly. The surface of all the myocardial cells studied contained abundant sialic acid distributed in two distinct layers, one in the surface coat next to the lipid bilayer, the other in the external lamina at the interstitial interface. The removal of sialic acid from the cellular surface increases calcium (Ca) exchangeability 5to 6-fold. Its removal also permits La to enter the cell and displace more than 80% of cellular Ca. Despite these marked alterations in Ca and La permeability, sialic acid removal has no effect on potassium

229 citations


Cites background from "Specific Uncoupling of Excitation a..."

  • ...exchangeable calcium, while eliminating further calcium exchange;(4) in the adult myocardium, lanthanum binding results in uncoupling of excitation from contraction.(5)...

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Journal ArticleDOI
TL;DR: The results support the idea that smaller ions enter the channel more slowly, presumably because they dehydrate more slowly; smaller ions also bind more tightly to a site within the channel pore, but lanthanide residence time within theChannel blockade approaches a maximum for the smaller cations with radii less than or equal to that of Ca2+.
Abstract: Currents flowing through single dihydropyridine-sensitive Ca2+ channels were recorded from cell-attached patches on C2 myotubes. In the presence of dihydropyridine agonist to prolong the duration of single-channel openings, adding micromolar concentrations of lanthanum (La), cerium (Ce), neodymium (Nd), gadolinium (Gd), dysprosium (Dy), or ytterbium (Yb) to patch electrodes containing 110 mM BaCl2 caused the unitary Ba2+ currents to fluctuate between fully open and shut states. The kinetics of channel blockade followed the predictions of a simple open channel block model in which the fluctuations of the single-channel current arose from the entry and exit of blocking ions from the pore. Entry rates for all the lanthanides tested were relatively insensitive to membrane potential, however, exit rates depended strongly on membrane potential increasing approximately e-fold per 23 mV with hyperpolarization. Individual lanthanide ions differed in both the absolute rates of ion entry and exit: entry rates decreased as cationic radius decreased; exit rates also decreased with cationic radius during the first part of the lanthanide series but then showed little change during the latter part of the series. Overall, the results support the idea that smaller ions enter the channel more slowly, presumably because they dehydrate more slowly; smaller ions also bind more tightly to a site within the channel pore, but lanthanide residence time within the channel approaches a maximum for the smaller cations with radii less than or equal to that of Ca2+.

195 citations


Cites background from "Specific Uncoupling of Excitation a..."

  • ...…inhibit contraction of the isolated frog heart, trivalent lanthanide cations have been shown to inhibit excitation-contraction coupling of cardiac (Sanborn and Langer, 1970) and smooth muscle (van Breeman, 1969; Mayer et al., 1972; Triggle and Triggle, 1976), as well as transmitter release from…...

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Journal ArticleDOI
TL;DR: The results indirectly implicate stretch-activated channels in the genesis of stretch-induced arrhythmias and provide preliminary evidence for a potential new mode of antiarrhythmic drug action--blockade of stretch -activated channels.
Abstract: Transient diastolic dilatation of the isolated canine left ventricle predictably elicits arrhythmias. To test the hypothesis that such arrhythmias may be mediated by sarcolemmal stretch-activated channels, we attempted to inhibit stretch-induced arrhythmias with gadolinium (Gd3+), a potent stretch-activated channel blocker. In experiments with six isolated canine hearts, left ventricular volume was increased for 50 msec during early diastole and then returned to initial volume by a computerized servopump. The stretch volume was adjusted to yield a probability of eliciting a stretch-induced arrhythmia of 95 +/- 2% before treatment with Gd3+. When Gd3+ (1-10 microM) was administered, dose-dependent suppression of stretch-induced arrhythmias was observed. The probability of a stretch-induced arrhythmia was reduced to 13 +/- 10% (p less than 0.05) with 10 microM Gd3+. Washout of Gd3+ completely reversed this effect. Since Gd3+ is known to be a calcium channel antagonist, we compared the effect of Gd3+ on stretch-induced arrhythmias with that of verapamil and nifedipine. These calcium channel blockers produced no demonstrable inhibition of stretch-induced arrhythmias when administered at concentrations (1 microM) that substantially depressed left ventricular pressure development. Thus, our results indirectly implicate stretch-activated channels in the genesis of stretch-induced arrhythmias and provide preliminary evidence for a potential new mode of antiarrhythmic drug action--blockade of stretch-activated channels.

192 citations

References
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Journal ArticleDOI
TL;DR: A modification of the naphthalene-dioxane-PPO liquid scintillator has been described which will allow up to 3.0 ml of an aqueous solution to be counted as mentioned in this paper.

7,634 citations


"Specific Uncoupling of Excitation a..." refers methods in this paper

  • ...Three consecutive drops were collected in Beckman 20 ml glass scintillation vials, and 15 ml of Bray's solution (23) were added and the isotopic activity (cpm) measured by a Beckman model LS-200B scintillation spectrometer....

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Journal ArticleDOI

2,565 citations

Journal ArticleDOI
TL;DR: The author’s research has focused on the development of AlkalI-Cation SELECTIVITY in the context of a knowledge-based approach to decision-making in the rapidly changing environment.
Abstract: INTRODUCTION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ......... 582 ALKALI-CATION SELECTIVITY IN NONLIVING SySTEMS..... . . . . . . . . . . . . . . .. 583 ALKALI-CATION SELECTIVITY IN BIOLOGICAL SYSTEMS. . . . . . . . . . . . . . . . . . .. 587 THE ORIGIN OF ALKALI-CATION EQUILIBRIUM SELECTIVITY .. .. . .. . .... . \" 589 ANION SELECTIVITY. . . • . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 595 DIVALENT-CATION SELECTIVITY. . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . .. 599 OTHER IONS. . . . . .. . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 603 N ON-COULOMB FORCES, AND THE MEANING OF THE TRANSITION SEQUENCES 60S \"UNCHARGED\" MEMBRANES. . . . . . . . . . . . . . . . . . . . . . . . . . . . . • . . . . . . . . . . . . 607 DEGREE OF HYDRATION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 608 EFFECT OF SITE SPACING OR ION COORDINATION NUMBER. • . . . . . . . . . . . . .. 609 ENTROPY EFFECTS.... . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . .. 609 N ONEQUILIBRIUM SELECTIVITY. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 609 PORE RADIUS AND ALKALI-CATION SELECTIVITY.. . . . . . . . . . . . . . . . . . . .. ... 612 SUMMARY OF ION SELECTIVITY. • . . . • . . . . . . . . . . . . . . . . . . . . . . . . . . . . 614

635 citations


"Specific Uncoupling of Excitation a..." refers background in this paper

  • ...Diamond and Wright (31) found, from their experiments on gallbladder epithelium, that at pH 7 the epithelium was more permeable to cations than to anions, whereas at pH 2.4 the epithelium was more permeable to anions than to cations....

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  • ...However, this study together with the recent review by Diamond and Wright (30), in which the authors discuss the physical basis of a membrane's electrolyte and nonelectrolyte permselective properties , and the 1910 paper by Mines (20), in which he discusses the effects of Y, La, and Ce on frog ventricle and artificial membrane, do provide a rationale for further speculation....

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  • ...review by Diamond and Wright (30), in which the authors discuss the physi-...

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