Kv11.1 channel subunit composition includes MinK and varies developmentally in mouse cardiac muscle

The Kv11.1 (also ERG1) K(+) channel underlies cardiac I(Kr), a current that contributes to repolarization in mammalian heart. In mice, I(Kr) current density decreases with development and studies suggest that changes in the structure and/or properties of the heteromultimeric I(Kr)/Kv11.1 channel are responsible. Here, using immunohistochemistry, we report that total Kv11.1 alpha subunit protein is more abundant in neonatal heart and is distributed throughout both adult and neonatal ventricles with greater abundance in epicardia. Immunoblots reveal that the alpha subunit alternative splice variant, Kv11.1a, is more abundant in adult heart while the Kv11.1b variant is more abundant in neonatal heart. Additionally, MinK channel subunit protein is shown to co-assemble with Kv11.1 protein and is more abundant in neonatal heart. In summary, Kv11.1/I(Kr) channel composition varies developmentally and the higher I(Kr) current density in neonatal heart is likely attributable to higher abundance of Kv11.1/I(Kr) channels, more specifically, the Kv11.1b splice variant.     

Centrally and peripherally induced anosmia: influences on maternal behavior in lactating female rats.

Bilateral removal of the olfactory bulbs was found to produce deficits in several components of the maternal behavior of lactating, primiparous female rats. More dead pups were found in the cages of bilaterally bulbectomized females shortly after parturition than in the cages of unilaterally bulbectomized, sham operated, or unoperated females. Futhermore, bilaterally bulbectomized females showed deficits in pup retrieval relative to females in the other surgical conditions, and pups reared by bilaterally bulbectomized females weighed less at weaning than pups reared by females in the other surgical conditions. In contrast to bilateral bulbecomy, zinc sulphate treatments had no influence on pup mortality at parturition. However, zinc sulphate treated females did exhibit deficits in pup retrieval relative to saline treated females.     

锌对培养的乳鼠心肌细胞自发性搏动和电活动的影响

本文研究了不同浓度的Zn对培养的乳鼠心肌细胞自发性搏动及心肌细胞动作电位的影响。实验结果表明,加Zn在0.125—2ppm范围内,自发性搏动群落的出现率增高,与对照组比较,P<0.001。但Zn的浓度超过一定范围(4 ppm),自发搏动率则呈降低趋势;8 ppm组明显低于对照组,P<0.01.Zn对心肌细胞动作电位的影响表现为动作电位的发放频率减慢,波幅降低,波宽变窄和最大除极速度减慢。     

Zinc ions in beta-cells of obese, insulin-resistant, and type 2 diabetic rats traced by autometallography

Zinc ions in the secretory granules of beta-cells are known to glue insulin molecules, creating osmotically stable hexamers. When the secretory granules open to the surface, the zinc ion pressure decreases rapidly and pH levels change from acid to physiological, which results in free insulin monomers and zinc ions. The released zinc ions have been suggested to be involved in a paracrine regulation of alpha- and beta-cells. Since zinc is intimately involved in insulin metabolism and because zinc homeostasis is known to be disturbed in type 2 diabetes, we decided to study the ultrastructural localisation of zinc ions in insulin-resistant and type 2 diabetic rats as compared to controls. By means of autometallography, the only method available for demonstrating zinc ions at ultrastructural levels, we found zinc ions in the secretory granules and adjacent to the plasma membrane. The membrane-related staining outside the plasma membrane reflects release of zinc ions during exocytosis. No apparent difference was found in the ultrastructural localisation of zinc ions when we compared the obese Zucker (fa/fa) rats, representing the insulin resistance syndrome, and the GK rats, representing type 2 diabetes, with controls. This suggests that the ultrastructural localisation of zinc ions is unaffected by the development of type 2 diabetes in rats in a steady state of glycaemia.     

锌对肝缺血再灌注损伤的对抗作用及其机制研究

目的:观察外源性锌对缺血再灌注肝脏(HIR)的防护作用并探讨其机制,包括对粘附分子表达的影响。方法:复制大鼠HIRI模型,灌胃给锌,观察实验动物肝组织形态、血清转氨酶活性、血清丙二醛(MDA)含量及粘附分子表达的改变。结果:在肝脏缺血30min,再灌注90min时,大鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)活性增高,肝细胞结构受损,血清MDA含量升高,肝组织中细胞间粘附分子-1(ICAM-1)和血管细胞粘附分子-1(VCAM-1)两种粘附分子表达增强;锌+缺血再灌注组大鼠血清GPT、GOT活性及血清MDA含量均明显低于缺血再灌注组,肝组织粘附分子表达亦较弱,肝细胞的结构基本正常。结论:外源给锌可以明显减轻肝脏缺血再灌注损伤,抗脂质过氧化和抑制粘附分子表达是其作用的重要机制。     

Effects of parathyroid hormone and calcitonin on Na+, Cl−, K+, Mg2+ and Ca2+ transport in cortical and medullary thick ascending limbs of mouse kidney

The effect of parathyroid hormone (PTH) on transepithelial Na⁺, Cl^–, K⁺, Ca²⁺ and Mg²⁺ transport was investigated in isolated perfused cortical thick ascending limbs (cTAL) and that of human calcitonin (hCT) was tested in both cortical and medullary thick ascending limbs (mTAL) of the mouse nephron. The transepithelial ion net fluxes (J _x) were determined by electron probe analysis of the perfused and collected fluids. Simultaneously, the transepithelial voltage (PD_te) and resistance (R _te) were recorded. In cTAL segments, PTH and hCT significantly stimulated the reabsorption of Na⁺, Cl^–, Ca²⁺ and Mg²⁺. hCT generated a net K⁺ secretion towards the lumen and PTH tended to exert the same effect. Neither PD_te nor R _te were significantly altered by either PTH or hCT. However, in the post-experimental period a significant decrease in PD_te was noted. Time control experiments carried out under similar conditions revealed a significant decrease in PD_te with time, which could have masked the hormonal response. In mTAL segments, Mg²⁺ and Ca²⁺ transport was close to zero. hCT did not exert any detectable effect on either PD_te or J _Cl ^–, J _Na ⁺ J _K ⁺, J _Mg ²⁺ and J _Ca ²⁺ in these segments. In conclusion, our data demonstrate that PTH and hCT stimulate NaCl reabsorption as well as Mg²⁺ and Ca²⁺ reabsorption in the cTAL segment of the mouse. These data are in agreement with and extend data obtained in vivo in the rat.     

Zinc Transport through Residual Bodies in the Rat Testis; a Histochemical Study

The aim of the present report was to study the zinc localization in rat testis with the help of a modified selective histochemical method (dithizone method). To achieve a selective demonstration of zinc, 16 microns thick serial cryostat sections of the Wistar rat testis were incubated with dithizone solution followed by a treatment with a "complexing buffer". PAS-reaction with haematoxylin was performed to determine the stages of spermatogenesis. During the maturation phase (from stage III onwards) the red coloured zinc dithizonate granules are observed in the mid piece and tail of elongated spermatids; the number and the stain intensity of zinc granules increase continuously till the stage VII. During the stages IX--X the zinc granules, present in the residual bodies, migrate from the adluminal to the basal Sertoli cell compartment. Thereafter, the zinc granules are observed only in the boundary tissue till the stage XIV. The results lead to suggest that the residual bodies play an essential role in the zinc transport.     

Increased sensitivity of mice to tremorogenic agents following MPP+

The behavioral effects following intrastriatal MPP⁺, the neurotoxic metabolite of MPTP, were evaluated in mice. Bilateral injections of 10 cro;g MPP⁺ to mice previously trained in the shuttle box paradigm produced a 66% decrease in striatal dopamine and significant deficits in all measures of conditioned avoidance responding. In addition, although these mice showed no deficits in baseline rotorod performance, challenge with the cholinergic agonist oxotremorine revealed that MPP⁺-treated mice exhibited an increased sensitivity to the disruptive effects of the drug at each dose and time point. Finally, MPP⁺-treated mice also exhibited an increase in tremor induced by 0.1 and 0.15 mg/kg oxotremorine. These observations are discussed in reference to idiopathic parkinsonism.     

Effects of cadmium exposure on zinc and copper distribution in neonatal rats

Tissue zinc and copper concentrations undergo marked changes in the neonatal rat during the first several weeks of life and it was of considerable interest to study the effect of cadmium exposure on these ontogenic changes. Long evans rats received either 2 or 10 mol cadmium chloride per kg SC at 9 days of age and were sacrificed at 20 or 36 days of age. Tissue copper and zinc concentrations in cadmium-treated rats were compared to those of age-matched controls for statistically significant changes. The tissue affected, the element altered and the direction of change in concentration, increased (+) or decreased (-), are summarized for the two dosing groups (age at dosing, age at sacrifice in days): 2 mol/kg (9, 20): kidney Zn (+), blood Zn (-), cerebral Cu (-), cerebellar Cu (+); 2 mol/kg (9, 36): blood Zn (-); 10 mol/kg (9, 20); liver, kidney, cerebral and cerebellar and blood Zn (-), cerebellar Cu (+); 10 mol/kg (9, 36]: liver and heart Zn (+), blood Zn (-); liver and heart Zn (+), blood Zn (-); kidney, cerebral, cerebellar and heart Cu (+). Changes in tissue zinc or copper concentrations produced by cadmium treatment could not be accounted for by the direct replacement of these elements by cadmium and may be due to alterations in transport of these elements. These results indicate that early life exposure to low levels of camium can have large and persistent effects on the distribution of the essential metals, copper and zinc.     

New detection schemes in liquid chromatography

A micropolarimeter interfaced to a liquid chromatograph is shown to be suitable for selective monitoring of the optically-active components in complex samples. When an optically-active eluent is used, indirect determination of even optically-inactive materials is possible, down to the level of 10 ng of an injected component. If a second chromatogram is obtained using the racemic analogue of the optically-active eluent, quantitation can be achieved without standards and without prior analyte identification. This concept is also applicable to the refractive index detector, the absorption detector and the conductivity detector in the special case of ion chromatography, and the ultrasonic detector in gas chromatography.