Total sialic acid profile in regressing and remodelling organs during the metamorphosis of marsh frog (Pelophylax ridibundus Pallas 1771)

This study aimed to investigate the functional relationship of sialic acid in regressing and remodelling organs such as the tail, small intestine and liver during the metamorphosis of Pelophylax ridibundus. For this purpose, four groups were composed according to developmental periods by considering Gosner's criteria (1964). Our findings showed that the sialic acid content of the larval tail has an opposite profile to cell death process. Although the sialic acid content of the small intestine and liver did not change evidently during metamorphosis, it increased after the completion of metamorphosis. Frog tail extensively exhibited cell death process and decreased proliferative activity and underwent complete degeneration during metamorphic climax. In spite of increased apoptotic index, a decreased sialic acid level in the tail tissues during climax can be the indication of a death cell removal process. However, the intestine and the liver included both cell death and proliferative process and remodelling in their adult forms. Thus, their sialic acid profiles during metamorphosis were different from the tail's profile. These data show that sialic acid may be an indicator of the presence of some cellular events during metamorphosis and that it can have different roles in the developmental process depending on the organ's fate throughout metamorphosis. Copyright © 2012 John Wiley & Sons, Ltd.     

A calcium channel blocker flunarizine attenuates the neurotoxic effects of iron

Iron is a metal highly concentrated in liver and brain tissue, and known to induce neuronal hyperactivity and oxidative stress. It has been established that iron levels rise in the brain in some neurodegenerative diseases such as Parkinson's and Alzheimer's diseases (AD). A body of evidence indicates a link between neuronal death and intracellular excessive calcium accumulation. The aim of the present study was to investigate the effects of a calcium antagonist, flunarizine, on neurotoxicity induced by intracerebroventricular (i.c.v.) iron injection. For this reason rats were divided into three groups as control, iron and iron+flunarizine groups. Animals in iron and iron+flunarizine groups received i.c.v. FeCl₃ injection (200 mM, 2.5 μl), while control rats received the same amount of saline into the cerebral ventricles. Rats in iron+flunarizine group also received i.c.v. flunarizine (1 μM, 2 μl) following FeCl₃ injection. All animals were kept alive for ten days following the operation and animals in iron+flunarizine group received intraperitoneal (i.p.) flunarizine injections once a day (10 mg/kg/day) during this period. After ten days, rats were sacrificed. The total numbers of neurons in hippocampus of all rats were estimated with the latest, unbiased stereological techniques. Findings of the present study suggest that flunarizine may attenuate the neurotoxic effects of iron injection by inhibiting the cellular influx of excessive calcium ions.     

Effect of various beta-adrenolytic drugs and calcium channel blocker (nifedipine) on selected indicators of calcium-phosphorus metabolism in patients with hyperthyroidism and simple goiter

The study was aimed at evaluation of the effect of short-term treatment with one of the six beta adrenolytic drugs (propranolol, metoprolol, atenolol, pindolol, nadolol, acebutolol) and calcium antagonist nifedipine on the values of several parameters of calcium-phosphorus metabolism in 81 patients with hyperthyroidism (14 patients with Graves' disease, and 67 patients with toxic nodular goiter), and 82 patients with simple goiter. The patients studied have been divided into seven groups, each receiving one of the investigated drugs during four days. A significant decrease in the urinary excretion of hydroxyproline was found only in the patients with hyperthyroidism receiving propranolol. This effect of propranolol on hydroxyprolinuria was not related to the degree of lowering of serum T3 concentration observed in these patients.     

Effects of calcium preloading on the growth of calcium carbonate crystals in the endolymphatic sac of the tree frog,Hyla arbores japonica

Summary Tree frogs, either with or without calcium chloride preloading, were maintained in a 0.8% strontium chloride solution for 1 week, then studied by X-ray microanalysis and scanning electron microscopy to determine the distribution of incorporated strontium in the endolymphatic crystals. In the absence of calcium preloading, strontium was detected on every surface of all the crystals, but after calcium preloading for 5 or 7 weeks, strontium incorporation was partially or completely inhibited, suggesting that an inhibition of the growth of the endolymphatic crystals had taken place in these preloaded specimens.     

Influence of temperature on the spatial distribution of first spawning dates of the common frog (Rana temporaria) in the UK

Between 1998 and 2007, the UK Phenology Network collected nearly 70 000 records of the first spawn dates of the common frog Rana temporaria . Annual national mean dates varied by more than 2 weeks and were closely related to January–March temperatures. A 1 °C increase in Central England Temperature advanced national mean spawning by 5.1 days. The temporal pattern of spawning records varied between years; sometimes unimodal in form, sometimes multimodal, seemingly associated with steady or erratic rises in spring temperatures, respectively. Spatial patterns of frogspawn were similar in different years, the earliest records occurring in the southwest with records progressively later in the north and east. On average, 100 km of eastwards progression took 7.4 days and 100 km of northwards progression took 4.7 days. A composite map for the 1998–2007 period is constructed and compared with an earlier published map based on data 60 years previously. The similarity and dissimilarity of these two maps is discussed; the general progression pattern of frogspawn phenology is similar but an advance of a 10-day contour category is apparent. We anticipate further advances of frog spawning dates in the future and an increase in the numbers of pre-January 1 records of frog breeding.     

Effects of calcium on the gramicidin A single channel in phosphatidylserine membranes

In phosphatidylserine membranes the decrease in the conductance of the gramicidin A single channel caused by calcium is attributed to a reduction of surface potential and to a direct blocking of the pore (Apell et al. 1979).The aim of this paper is to make a, quantitative evaluation of these two effects. We recorded the conductance of gramicidin single channels in 100 mM KCl in the presence of different amounts of CaCl₂, MgCl₂ or TEACl.The ionic activities at the channel mouth were calculated using the Gouy-Chapman-Stern theory. Our experiments showed that even when the K⁺ activity at the channel mouth was estimated to be the same, the single channel conductance was lower if divalent cations were present. This effect is attributed to a blocking action of these ions.Abbreviations PS phosphatidylserine - TEA tetraethylammonium     

A comparison of the effects of phytohaemagglutinin and of calcium ionophore A23187 on the metabolism of glycerolipids in small lymphocytes.

1. The effects of phytohaemagglutinin and of a Ca2+ ionophore (A23187) on glycerolipid metabolism in lymphocytes from pig lymph nodes were compared (a) by studying the incorporation of [32P]Pi and [3H]glycerol, and (b) by following the redistribution of [3H]glycerol among the lipids caused by these agents in pulse-chase experiments. 2. Phytohaemagglutinin only stimulated 32P incorporation into phosphatidylinositol and, to a slight extent, phosphatidate. Removal of most of the extracellular Ca2+ somewhat decreased this response. 3. Ionophore A23187 stimulated the labelling of phosphatidate and phosphatidylinositol with 32P to a much greater extent than did phytohaemagglutinin: the increase in phosphatidate labelling, but not that of phosphatidylinositol, was almost abolished by the removal of extracellular Ca2+. 4. The combined effects of phytohaemagglutinin and ionophore appeared to be additive, rather than synergistic. 5. Treatment with ionophore A23187 somewhat decreased the total incorporation of [3H]glycerol into glycerolipids, possibly because it lowered cell ATP content. In these experiments di- and tri-acylglycerol behaved anomalously, triacylglycerol labelling being suppressed completely, whereas that of diacylglycerol was enhanced. The pulse-chase results revealed that triacylglycerol was converted into diacylglycerol in the ionophore-treated cells, and the availability of this diacylglycerol probably led to the enhanced labelling of phosphatidate and phosphatidylinositol in the these cells. 6. Thus an increase in intracellular Ca2+ concentration appeared to have three effects on glycerolipid metabolism: (a) slight inhibition of some metabolic step preceding phosphatidate synthesis, (b) inhibition of diacylglycerol acyltransferase and (c) activation of a triacylglycerol lipase. 7. In contrast, it seems likely that the only effect of phytohaemagglutinin is to stimulate phosphatidylinositol breakdown. 8. Pig polymorphonuclear leucocytes treated with ionophore A23187 showed metabolic changes that were similar to those demonstrated with lymphocytes. 9. A possible similarity is suggested between Ca2+-stimulated triacylglycerol lipase in lymphocytes and polymorphonuclear leucocytes and previous observations of enhanced triacylglycerol metabolism in stimulated cells whose metabolic functions involve membrane fusion.     

Effects of the iron chelator deferiprone and the T-type calcium channel blocker efonidipine on cardiac function and Ca2+ regulation in iron-overloaded thalassemic mice

Although disturbance of cardiac Ca²⁺ regulation is involved in the pathophysiology of iron-overload cardiomyopathy, the obvious mechanisms involved in the dysregulation of iron-induced cardiac Ca²⁺ are unclear. Moreover, the roles of the iron chelator deferiprone and the T-type calcium channel blocker efonidipine on cardiac intracellular Ca²⁺ transients and Ca²⁺ regulatory proteins in thalassemic mice are still unknown. We tested the hypothesis that treatment with either deferiprone or efonidipine attenuated cardiac Ca²⁺ dysregulation and led to improved left ventricular (LV) function in iron-overloaded thalassemic mice. Wild-type (WT) mice and β-thalassemic (HT) mice were fed with either a normal diet (ND) or a high iron-diet (FE) for 90 days. Then, the FE-fed mice were treated with either deferiprone (75 mg/kg/day) or efonidipine (4 mg/kg/day) for 30 days. ND-fed HT mice had an increase in T-type calcium channels (TTCC) and an increased level of sarcoplasmic reticulum Ca²⁺-ATPase (SERCA), compared with ND-fed WT mice. Chronic iron feeding led to an increase in TTCC and expression of SERCA proteins in FE-fed WT mice. Moreover, chronic iron overload led to increased plasma non-transferrin bound iron (NTBI) and cardiac iron deposition, impaired cardiac intracellular Ca²⁺ transients including decreased intracellular Ca²⁺ transient amplitude, rising rate and decay rate, as well as impaired LV function as indicated by a decreased %LV ejection fraction (%LVEF) in both WT and HT mice. Our findings showed that treatment with either deferiprone (DFP) or efonidipine (EFO) showed similar benefits in reducing plasma NTBI and cardiac iron deposition, and improving %LVEF from 84.3 (WT) to 89.3 (DFP) and 89.2 (EFO) treatment; and from 84.2 (HT) to 88.8 (DFP) and 89.5 (EFO) treatment, however there was no improvement in the regulation of cardiac Ca²⁺ in iron-overloaded thalassemic mice. These findings provide the understanding of the effects of these drugs on the iron-overloaded heart in thalassemic mice and suggest that an alternative intervention that could improve calcium regulation under this condition is needed to improve the therapeutic outcome. Moreover, whether the benefits of the TTCC blocker is via its inhibition of the TTCC alone or together with its ability to chelate iron are still unclear and need further investigation.     

Effects of the calcium channel blocker amlodipine on serum and aortic cholesterol,lipid peroxidation,antioxidant status and aortic histology in cholesterol-fed rabbits

Reactive oxygen metabolites and oxidized fatty acids are proinflammatory and are involved in the pathophysiology of atherosclerosis. Amlodipine, a unique third-generation dihydropyridine-type calcium channel blocker, seems to exert atheroprotective effects through its antioxidant properties related to its chemical structure and independent of its calcium channel-blocking effect. In this study, the interactions of amlodipine with major cellular antioxidants were investigated in order to elucidate the mechanisms underlying its atheroprotective effects. New Zealand white male rabbits were fed regular chow (group 1), chow with 1% cholesterol (group 2), regular chow plus 5 mg/kg/day amlodipine per os (group 3) and 1% cholesterol plus amlodipine (group 4) for 8 weeks. Total cholesterol, malondialdehyde (MDA) and vitamin E concentrations and catalase and superoxide dismutase (SOD) activities were determined in blood drawn before and after the experimental period. Aortic tissue was examined for atherosclerotic changes and aortic total cholesterol, MDA, catalase and SOD were determined. At the end of the 8-week treatment period, serum total cholesterol and plasma MDA were elevated in groups 2 and 4. In group 2, serum vitamin E and plasma SOD diminished (p < 0.05) and catalase increased (p < 0.05). In group 4, SOD activity increased at the end of treatment. MDA levels were lower and plasma SOD activities were higher in group 4 than in group 2. Aortic tissue investigations revealed higher total cholesterol and MDA concentrations and catalase activities in group 2 than in group 4, and the highest tissue SOD activity was recorded in group 4 (p < 0.05 for all comparisons). Morphological examination of aortic tissues exhibited endothelial disarrangement and lipid deposition in group 2. Histopathological alterations related to atherogenesis were less in group 4 than in group 2. Amlodipine seems to exert atheroprotective effects by reducing aortic cholesterol accumulation and blood and aortic lipid peroxidation, enhancing SOD activity both in blood and aortic tissue and suppressing the consumption of vitamin E. On the other hand, the suppression of catalase activity in blood and the aorta interferes with the drug's well-known antioxidant effects.     

Differential effects of glycolytic and oxidative metabolism blockers on the Na-K pump in erythrocytes of the frog, Rana temporaria

This study was undertaken to evaluate the effects of various metabolic blockers on the Na-K-pump activity and ATP content of frog erythrocytes. To eliminate K-C1 cotransport, the frog erythrocytes were incubated in nitrate media at 20 °C. Incubation of the red cells in a glucose-free medium for 2 h had no effect on cell ATP content and K⁺ influx measured as ⁸⁶Rb uptake for 60 min. The Na⁺-K⁺-pump activity was also unchanged in the frog erythrocytes incubated in a glucose-free medium containing 10 mM 2-deoxy-D-glucose or adenosine. Unexpectedly, the treatment of red cells with 1–2 mM glycolytic blocker iodoacetate produced a 2-fold increase in the ouabain-sensitive K⁺ influx. The cell ATP content declined by 9.4% after 2 h of cell incubation with iodoacetate. Incubation of the red cells for 90 min in the presence of 2 mM cyanide, 0.01 mM antimycin A or 5 mM azide resulted in a significant reduction in K⁺ influx by about 50%, 45% and 32%, respectively. The cell ATP content diminished over 60 min and 120 min of cell incubation with 2 mM cyanide by 15.6% and 31.7% of control levels, respectively. In time-course experiments, a 50% reduction in the K⁺ influx was observed when the frog erythrocytes were incubated for only 30 min in the presence of 2 mM cyanide. In contrast, 0.01–0.10 mM rotenone, a site I inhibitor, and 0.01 mM carbonyl cyanide m-chlorophenylhydrazone, an uncoupler of oxidative phosphorylation were without effect on K⁺ influx into frog erythrocytes. These results indicate that about one-half of the Na⁺ -K⁺-pump activity in frog erythrocytes is tightly functionally coupled to cytochromes via a separate “membrane-associated” ATP pool. Accepted: 12 July 1997     

The effects of calcitonin on plasma calcium levels and bone metabolism in the fresh water teleost Channa punctatus

Administration of salmon calcitonin (sCT) caused significant reduction in total and ultrafiltrable plasma calcium content in the plasma of a fresh water female teleost Channa punctatus. A time-bound analysis on the effect of sCT showed a highly significant short duration reduction in total and ultrafiltrable plasma calcium content in fish kept in normal tap water and low-calcium water and a moderate hypocalcemia in fish kept in high-calcium water. Sexually immature adult fish showed a greater response than the sexually mature ones. Using tartrate-resistant acid phosphatase (TRACP) and alkaline phosphatase (ALP) activities in plasma and hydroxyproline (HYP) excretion in urine, the effect of sCT on the inhibition of bone calcium resorption were examined. In both sexually mature and immature adult fish, kept in normal tap water, sCT significantly suppressed TRACP and ALP activities in plasma and excretion of HYP in urine within 2-6 h with a maximum at 4 h after injection. Salmon CT treatment to sexually immature adult fish caused significant increase in skeletal bone calcium concentration. Taken together, all this information indicates that CT in a fresh water female teleost is an effective regulator of plasma calcium levels, and its action, at least in part, operates through inhibition of bone calcium resorption.     

ERK1/2通路在低氧上调大鼠PASMCs钙激活性氯离子通道表达的作用

目的：探讨钙激活性氯离子通道（CLCA2）在大鼠低氧性肺动脉平滑肌细胞（PASMCs）中mRNA和蛋白表达的变化及其与ERK1/2信号通路的关系。方法：PASMCs随机分为：常氧组（N组）,低氧组（H组）,DMSO对照组（D组）,U0126干预组（U组）,Staurosporine aglycone干预组（SA组）,采用免疫印迹法检测CLCA2蛋白的表达;选用半定量逆转录-聚合酶链反应（RT-PCR）技术测定CLCA2 mRNA水平的表达。结果：PASMCs中CLCA2 mRNA和蛋白的表达量,H组较N组明显上调（P<0.01）;U组较D组明显上调（P<0.01）;SA组较D组mRNA的表达显著下调（P<0.01）,蛋白的表达轻微下调。结论：低氧可上调CLCA2中mRNA和蛋白在PASMCs的表达;ERK1/2通路激活剂-Staurosporine aglycone能下调CLCA2在PASMCs中mRNA和蛋白的表达量;ERK1/2通路抑制剂-U0126可上调CLCA2在PASMCs中mRNA和蛋白的表达量。     

The effects of infection by Phytophthora infestans on the control of phenylpropanoid metabolism in wounded potato tissue

During the first 24 h of in vitro incubation of excised potato tuber (Solanum tuberosum L.) discs, the appearance of phenylalanine ammonia-lyase (PAL; EC 3.4.1.5) and the accumulation of chlorogenic acid are both stimulated by infection with Phytophthora infestans (Mont.) de Bary. Whereas in control tissue the level of PAL reached a stable plateau value after 40 h, in infected tissue it subsequently rose again, in one experiment, as the fungal mycelium developed. In the infected but not the control tissue, the level of chlorogenic acid subsequently fell to about to about 20% of its maximum after 50 h. The time courses of increases in cinnamic acid 4-hydroxylase (CA4H; EC 1.14.13.11; 0–60 h) and of caffeic acid acid o-methyltransferase (COMT; EC 2.1.1.42; 0–160 h) are not altered by fungal infection. If the discs are restored to the tuber environment immediately after excision, by placing them inside a host tuber, the activity of PAL as well as those of CA4H and COMT remained at the constant low endogenous level for at least 60 h, irrespective of whether the discs had first been inoculated with P. infestans. The increase in PAL may not be an obligatory feature of the P. infestans/potato compatible interaction but dependent on an underlying wound response. The experiments provide further evidence that PAL is the rate limiting step of chlorogenic acid biosynthesis in potato tuber discs.Abbreviations PAL phenylalanine ammonia-lyase - CA4H cinnamic acid 4-hydroxylase - COMT caffeic acid o-methyltransferase - CGA chlrogenic acid (5-o-caffeoylquinic acid) - gfwt gram fresh weight     

The effects of calcium ions, ionophore A23187 and inhibition of energy metabolism on protein degradation in the rat diaphragm and epitrochlearis muscles in vitro.

1. The effects of external Ca2+, EGTA, ionophore A23187, CN-, dinitrophenol and iodoacetamide on the rate of protein degradation in the rat diaphragm and epitrochlearis muscles in vitro were investigated. 2. External Ca2+ increased protein degradation when compared with external EGTA. Protein degradation was further increased by Ca2+ + ionophore A23187. 3. EGTA and ionophore A23187 decreased ATP and phosphocreatine concentrations and the ATP/ADP ratio. 4. CN-, dinitrophenol and iodoacetamide decreased protein degradation, presumably by interfering with energy metabolism. 5. The effects of EGTA may be caused by disturbances in energy metabolism. The effects of ionophore A23187 cannot be readily explained by disturbances in energy metabolism. 6. Incubation of diaphragms with Ca2+ causes a rapid increase in whole-tissue Ca content. This is further stimulated by ionophore A23187. The uptake of Ca2+ may be, at least in part, into the cytoplasm because an increase in the glycogen phosphorylase activity ratio is observed. 7. A Ca2+-activated proteinase is present in rat heart and diaphragm. This enzyme may mediate in part the effects of Ca2+ described above. The apparent KA of this enzyme for Ca2+ is about 0.25 mM. 8. Because effects of ionophore A23187 cause a large increase in whole-tissue Ca content and because the Ca2+-activated proteinase has a relatively low affinity for Ca2+, it is felt that the effects of Ca2+ upon muscle proteolysis are unlikely to be of importance in steady-state protein turnover in vivo. The mechanism may, however, be important in breakdown of necrotic tissue in the living animal.     

Effects of the calcium ionophore A 23187 on low-density lipoprotein processing and lipid metabolism in cultured human fibroblasts

Pretreatment of cultured human fibroblasts with the calcium ionophore A 23187 resulted in a decrease in low-density lipoprotein internalization. This effect was dose-dependent and did not occur in a medium devoid of calcium. About 2-fold reduction was observed with 10(-5)M A 23187. In contrast, the low-density lipoprotein binding was only slightly affected. The incorporation of [14C]acetate and [14C]oleate into all classes of lipids (sterol, triacylglycerols and phospholipids) was strikingly reduced by ionophore pretreatment.     

A comparison of the effects of chromate,molybdate and cadmium oxide on respiration in the yeastSaccharomyces cerevisiae

Summary Growth ofSaccharomyces cerevisiae on non-fermentable medium was more sensitive to inhibition by chromate than growth on fermentable medium. Chromate was selectively toxic against oxygen uptake in cells grown in non-fermentable medium and also inducedpetite mutations. CdO demonstrated similar but lesser effects on growth and respiration. However, molybdate had little toxicity to yeast non-fermentable growth and stimulated oxygen uptake in cells grown in fermentable and non-fermentable media. These results suggest that chromate, a carcinogen, may act more directly against the mitochondria ofS. cerevisiae than related chemical species, CdO and molybdate.     

A fish bradykinin (Arg0, Trp5, Leu8-bradykinin) from the defensive skin secretion of the European edible frog, Pelophylax kl. esculentus: structural characterization; molecular cloning of skin kininogen cDNA and pharmacological effects on mammalian smooth muscle

Extensive studies on bradykinin-related peptides (BRPs) generated from plasma kininogens in representative species of various vertebrate taxa, have confirmed that many amphibian skin BRPs reflect those present in putative vertebrate predators. For example, the (Val¹, Thr⁶)-bradykinin, present in the defensive skin secretions of many ranids and phyllomedusines, can be generated from plasma kininogens in colubrid snakes—common predators of these frogs. Here, we report the presence of (Arg⁰, Trp⁵, Leu⁸)-bradykinin in the skin secretion of the European edible frog, Pelophylax kl. esculentus, and have found it to be encoded in single copy by a kininogen with an open-reading frame of 68 amino acid residues. This peptide is the archetypal bony fish bradykinin that has been generated from plasma kininogens of the bowfin (Amia calva), the long-nosed gar (Lepisosteus oseus) and the rainbow trout (Onchorhynchus mykiss). More recently, this peptide has been shown to be encoded within cloned kininogens of the Atlantic cod (Gadus morhua) spotted wolf-fish (Anarichas minor), zebrafish (Danio rerio), pufferfish (Tetraodon nigroviridis) and Northern pike (Esox lucius). The latter species is regarded as a major predator of P. kl. esculentus. Synthetic (Arg⁰, Trp⁵, Leu⁸)-bradykinin was previously reported as having multiphasic effects on arterial blood pressure in conscious trout and here we have demonstrated that it can antagonize the relaxation in rat arterial smooth muscle induced by canonical mammalian bradykinin. The discovery of (Arg⁰, Trp⁵, Leu⁸)-bradykinin in the defensive skin secretion of this amphibian completes the spectrum of vertebrate taxon-specific BRPs identified from this source.     

A comparative study of the effects of Pr<Superscript>3+</Superscript> and La<Superscript>3+</Superscript> ions on calcium dependent processes in frog cardiac muscle and rat heart mitochondria

The inotropic effect of Pr³⁺ and La³⁺ ions on the heart muscle of frog Rana ridibunda, as well as the influence of the ions on respiration, swelling, and the potential (ΔΨ_mito) on the inner membrane of Ca²⁺- loaded rat heart mitochondria, energized by glutamate and malate or succinate in the presence of rotenone were studied. It was found that 2 mM Pr³⁺ in Ringer’s solution reduces the force of spontaneous contractions and those induced by electrical stimulation in the heart; it had a negative chronotropic effect, decreasing the frequency of spontaneous contractions. Pr³⁺ and La³⁺ prevented a decrease in the 2,4-dinitrophenol (DNP)- uncoupled respiration of energized rat heart mitochondria, swelling of these organelles in salt media, and a reduction in ΔΨ_mito on the inner mitochondrial membrane that were induced by Ca²⁺ ions. Retardation by Pr³⁺ and La³⁺ ions of these calcium-induced effects may suggest that in the inner mitochondrial membrane these metals inhibit the opening of the mitochondrial permeability transition pore caused by Ca²⁺ overload of mitochondria. The data we obtained are important for a better understanding of the mechanisms of the damaging action of rare-earth elements on Ca²⁺-dependent processes in the vertebrate myocardium.