Transmembrane calcium transport and the activation of cardiac contraction

It has been known for a century that extracellular Ca2+ ions are needed for triggering contraction in the heart. However, the two possible mechanisms of Ca2+ entry into the cardiac cells have only been discovered and investigated recently: these are the voltage-gated Ca2+ channels and the Na+-Ca2+ exchange. This paper reviews the field of the control of cardiac contractility by the sarcolemma and describes various techniques used to study the Ca2+ transport and the corresponding two components of contraction: phasic and tonic tension. The most controversial issue of the past 5 years, attracting the attention of many investigators, is whether or not the Na+-Ca2+ exchange in the heart is electrogenic and voltage-dependent and thus contributes to the beat-to-beat regulation of free intracellular [Ca2+]. This paper concentrates on this controversy and gives an up-to-date view of the major steps in the development of our present concept of this transport and of some of the recent experimental approaches. The contribution of an electrogenic, voltage-dependent Na+-Ca2+ exchange to the regulation of contraction, as well as to cardia electrical activity, is discussed, and the alterations of both of these cardiac functions due to Na+ accumulation intracellularly (owing to various interventions) are described.     

Platelet sensitivity to a prostacyclin analogue in normal and pathological pregnancy

Platelet sensitivity to a prostacyclin analogue (PSP) was investigated at different stages of normal and pathological pregnancies. During uncomplicated pregnancy PSP decreased progressively by about 30% and returned to almost normal values in the puerperium. In pre-eclamptic women PSP was reduced by 49% and in pregnant diabetics by 50% compared with normal pregnant individuals of corresponding gestational age. Reduced PSP in normal and pathological pregnancy seems to be another aspect of increased coagulability and platelet aggregation found in these patients.     

Dimensionality reduction for visualization of normal and pathological speech data

For an adequate analysis of pathological speech signals, a sizeable number of parameters is required, such as those related to jitter, shimmer and noise content. Often this kind of high-dimensional signal representation is difficult to understand, even for expert voice therapists and physicians. Data visualization of a high-dimensional dataset can provide a useful first step in its exploratory data analysis, facilitating an understanding about its underlying structure. In the present paper, eight dimensionality reduction techniques, both classical and recent, are compared on speech data containing normal and pathological speech. A qualitative analysis of their dimensionality reduction capabilities is presented. The transformed data are also quantitatively evaluated, using classifiers, and it is found that it may be advantageous to perform the classification process on the transformed data, rather than on the original. These qualitative and quantitative analyses allow us to conclude that a nonlinear, supervised method, called kernel local Fisher discriminant analysis is superior for dimensionality reduction in the actual context.     

Equine CTNNB1 and PECAM1 nucleotide structure and expression analyses in an experimental model of normal and pathological wound repair

Background  

Wound healing in horses is fraught with complications. Specifically, wounds on horse limbs often develop exuberant granulation tissue which behaves clinically like a benign tumor and resembles the human keloid in that the evolving scar is trapped in the proliferative phase of repair, leading to fibrosis. Clues gained from the study of over-scarring in horses should eventually lead to new insights into how to prevent unwanted scar formation in humans. cDNA fragments corresponding to CTNNB1 (coding for β-catenin) and PECAM1, genes potentially contributing to the proliferative phase of repair, were previously identified in a mRNA expression study as being up-regulated in 7 day wound biopsies from horses. The aim of the present study was to clone full-length equine CTNNB1 and PECAM1 cDNAs and to study the spatio-temporal expression of mRNAs and corresponding proteins during repair of body and limb wounds in a horse model.     

Contact microscopic and histochemical studies of the placenta in normal and pathological pregnancy]

The placenta was studied in 70 women: 19 of them had physiological pregnancy and 51 had pregnancy complicated with late toxicosis. Lesions in the placenta have been shown to increase with the growing severity of toxicosis, and compensatory potencies--to decrease. In late toxicosis the expansion of desorganization and reparation in the placenta occurs from the center towards periphery, the peripheral parts playing the role of reserved zones of the placenta, keeping high functional activity.     

alpha 1-Microglobulin from normal and pathological urines

alpha 1-Microglobulin was purified from normal and pathological urines. Significant differences were found in the amino acid compositions of the alpha 1-microglobulin isolated from these two sources. In addition electrofocusing of alpha 1-microglobulin from normal urine gave rise to two peaks of equal intensity with rather acidic isoelectric points (3.8 and 4.2), whilst alpha 1-microglobulin from pathological urine showed two peaks in a 1:5 ratio with less acidic isoelectric points (4.2 and 4.7). Further charge heterogeneity was also observed in the second peaks from both sources. The sugar compositions were also established, as well as the N-terminal sequences of the alpha 1-microglobulin of both peaks isolated from normal and pathological urines.     

Ultrastructural and cytochemical localization of calcium in a rat cardiac muscle in normal and experimental conditions.

The experiment carried out by us on the, stimulated by adrenaline, cardiac muscle allowed the activation of calcium localized mainly in the mitochondria, MA and FA of the intercalated discs and SR to be translocated in the direction of the sarcomere myofilaments and this especially to the thin actin filaments. The authors' experimental proves, that during the contraction--relaxation function of the cardiac muscle there exists a circulation rythm or a oscillatory functional flow of calcium ions between the mitochondria, intercalated discs and SR and the contractile fibrillae of the sarcomere.     

Transmembrane transport of fatty acids in the heart

Summary Although fatty acid uptake by the myocardium is rapid and efficient, the mechanism of their transmembrane transport has been unclear. Fatty acids are presented to the plasma membrane of cardiomyocytes as albumin complexes within the plasma. Since albumin is not taken up by the cells, it was postulated that specific high affinity binding sites at the sarcolemma may mediate the dissociation of fatty acids from the albumin molecules, before they are transported into the cells. In studies with a representative long-chain fatty acid, oleate, it was in fact shown that fatty acids bind with high affinity to isolated plasma membranes of rat heart myocytes revealing a K_D of 42 nM. Moreover, a specific membrane fatty acid-binding protein (MFABP) was isolated from these membranes. It had a molecular weight of 40 kD, an isoelectric point of 9.0, and lacked carbohydrate or lipid components. Binding to a specific membrane protein might represent the first step of a carrier mediated uptake process. Therefore, the uptake kinetics of oleate by isolated rat heart myocytes was determined under conditions where only cellular influx and not metabolism occurred. Uptake revealed saturation kinetics and was temperature dependent which were considered as specific criteria for a facilitated transport mechanism. For evaluation whether uptake is mediated by MFABP, the effect of a monospecific antibody to this protein on cellular influx of oleate was examined. Inhibition of uptake of fatty acids but not of glucose by the antibody to MFABP indicated the physiologic significance of this protein as transmembrane carrier in the cellular uptake process of fatty acids. Such a transporter might represent an important site for the metabolic regulation of fatty acid influx into the myocardium.     

汞在微生物中的跨膜运输机制研究进展

甲基汞是一种强亲脂性、高神经毒性的有机汞化合物,可以通过生物富集或生物放大造成人类甲基汞暴露。环境中甲基汞的产生主要是厌氧微生物所调控的无机汞的甲基化。主流观点认为厌氧微生物对汞的甲基化是一种细胞内反应,因此,甲基汞的产生速率不仅与环境中具有汞甲基化能力的厌氧微生物的存在与活性相关,同时也与无机汞在微生物细胞中的跨膜运输过程有着重要联系。要明确无机汞经微生物甲基化的机制,就必须了解无机汞被微生物细胞生物吸收的过程,即无机汞在微生物中的跨膜运输路径。目前研究认为该过程主要有Mer抗汞操纵子转运体系、被动扩散、促进扩散和主动运输4种路径。本综述主要围绕无机汞被微生物细胞生物吸收的这4种路径展开,将系统介绍科学界对这4种路径的最新研究进展,并对相关研究进行展望,指出无机汞经促进扩散或主动运输进入到微生物细胞内将是未来研究的重点。     

Transmembrane electrical potential in Rickettsia prowazekii and its relationship to lysine transport.

The transmembrane electrical potential (delta psi) generated by Rickettsia prowazekii metabolizing glutamic acid or ATP was determined by flow dialysis with the lipophilic cation tetraphenylphosphonium and with lysine. At pH 7.0, the rickettsiae generated a delta psi as measured by tetraphenylphosphonium distribution of 90 mV. Under similar conditions, cells of R.prowazekii concentrated lysine to a gradient indicating a delta psi of 90 mV. Energy-starved cells of R. prowazekii were able to utilize exogenously supplied ATP as well as glutamic acid to generate a delta psi of 110 mV at pH 8.0. Lysine transport was markedly affected by environmental pH, the optimum pH ranging from 8.0 to 8.5. delta psi as measured with tetraphenyl-phosphonium was similarly affected in this system, with values ranging from 70 mV at pH 6.0 to 100 mV at pH 8.0. Respiration rates were also affected by the external pH, with a maximum rate of 28 nmol of O2 consumed per min per mg of rickettsial protein occurring at pH 8.0. The pH effects were readily reversible and with a rapid onset.     

Regulation of cellular calcium metabolism and calcium transport by calcitonin.

Calcitonin was studied in isolated kidney cells and in isolated mitochondria. A concentration of 10 ng/ml of synthetic calcitonin increases the cellular accumulation of 45Ca and the total cell calcium. The mitochondrial pool is increased several-fold. Kinetic analysis of the data shows that although the total cellular exchangeable calcium pool is enlarged, calcium influx and efflux are significantly depressed by calcitonin. The absence of phosphate or the presence of inhibitors of mitochondrial calcium transport completely abolish the effects of the hormone. In isolated mitochondria, the hormone stimulates the active calcium uptake and depresses the extramitochondrial calcium activity. Calcitonin counteracts the effects of cyclic AMP which stimulates the release of calcium from mitochondria and increases the extramitochondrial calcium activity. These data indicate that cellular calcium homeostasis is controlled by the mitochondrial calcium turnover. They suggest that calcitomin regulates the cell calcium metabolism and inhibits the transcellular calcium transport by stimulating the rate of calcium uptake by mitochondria which depresses cytoplasmic calcium activity.     

Transmembrane electron transport and the neutral theory of evolution

Based on the concept of pairs of basic functional states the evolution of the first chemiosmotic mechanism of energy conversion is discussed in terms of point mutations, gene duplications and of the neutral theory of evolution. A model for estimating the overall probability of the evolutionary step in question is presented, both for the selectionist and neutralist position. It is concluded that, concerning the present stage of knowledge, the evolution of transmembrane electron transport is an unsolved problem in evolutionary biology.