钩藤碱对心血管系统部分药理作用研究

探讨钩藤碱对钙离子的拮抗作用以及对脑血流量和氧消耗的作用。方法观察钩藤碱对豚鼠心肌的兴奋性、功能性不应期、正阶梯现象的作用，以及对去甲肾上腺素诱发的兔主动脉条Ⅰ、Ⅱ相收缩的作用，同时观察钩藤碱对小鼠氧消耗和大鼠脑血流量的影响。结果钩藤碱能提高心肌兴奋性，延长功能性不应期，抑制正阶梯现象和兔主动脉条Ⅰ、Ⅱ相收缩；减慢小鼠氧消耗速度，对大鼠脑血流量无影响。结论钩藤碱具有许多钙拮抗剂的共同特点，提示其在抗心律失常方面会有一定作用。     

The dependence of twitch relaxation on sodium ions and on internal Ca2+ stores in voltage clamped frog atrial fibres

Frog heart relaxation was analyzed under voltage clamp conditions as the tension decay observed after the membrane potential had been returned to its resting value. The tension decayed exponentially with a time constant of 188±3.8 ms SEM. The relaxation rate decreased with the external Na concentration. It fell to about one tenth in a Na-free solution. Increasing the intracellular Na-content by an application of veratrine also decreased the relaxation rate. Thus relaxation seems dependent on the Na gradient. The relaxation rate decreased within one second upon switching from a high to a low Na-containing solution. The relaxation rate reached a minimum before rising slightly to a new steady state value. This rebound may reflect the partial recovery of the Na gradient since a fast variation in [Na]_i follows alteration of [Na]_o. Mn and La ions also slowed relaxation. In a Na-free solution, adrenaline accelerated tension decay, an effect not noticeable in frog heart contained in Ringer solution. Other cAMP-promoting agents, such as dibutyryl-cAMP and aminophylline, also increased relaxation rate.It is concluded that in frog myocardium, part of the decrease of the intracellular Ca²⁺-concentration which occurs during each cardiac cycle could be dependent on a Na–Ca exchange mechanism. The relative importance of this mechanism, versus internal Ca sequestration, in the relaxation of tension may well be greater in contractile tissues whose cells have a large surface/volume ratio.     

Role of H+ ions in volume and voltage of epithelial cell nuclei

Condensation of chromatin depends upon the ion composition in the cell nucleus. We tested in isolated nuclei of Madin-Darby canine kidney cells the influence of various ions on nuclear volume (i. e. DNA packing) and intranuclear voltage. After isolation, nuclei were superfused with cytosolic solutions in which Na⁺, K⁺, Ca²⁺ and H⁺ ions were varied. With video-imaging and microelectrode techniques nuclear volume and intranuclear potential were measured in response to the various ions. In control cytosolic solution, isolated nuclei exhibited an intranuclear electrical potential of –6.5±0.5 mV (relative to a reference electrode in the cytosolic solution) corresponding to a nuclear volume of 250±10 fl (n=104). Changing the Na⁺, K⁺ or free Ca²⁺ concentration in the superfusate in the physiological range resulted in minor changes of volume and intranuclear potential whereas pH altered both parameters dramatically. Nuclear swelling and intranuclear negative voltage increased with alkalinization and decreased when pH was reduced. An intact nuclear envelope was found to be no prerequisite for maintaining intranuclear negativity, indicating that the composition and functional state of nuclear chromatin rather than specific ion permeabilities of the nuclear envelope determine nuclear electrical potential. We present a model that explains nuclear volume and voltage on the basis of interaction between negatively charged DNA and positively charged histones of the nuclear chromatin.     

Effects of training on iron status in cross-country skiers

Summary Haematological changes were studied in cross-country skiers during a 33-week training season (7 h a week). The daily amounts of training were calculated from the duration and the intensity of the exercise and then used to estimate training responses associated with a first order transfer function. The profile of system training responses (STR) was determined by convolution between the amounts of training and a first-order transfer function. Linear regressions were used to determine correlation coefficients between STR and iron status indices. Among the values for the time constants of decay, the one giving the best fit between STR and iron status indices was chosen. A relationship was noted between on the one hand STR and changes in serum ferritin concentration ([FERR]) and on the other hand STR and change in mean cell volume (MCV). The [FERR] was decreased and MCV was increased by training. It is suggested that a decrease in [FERR] could have been related to a decrease in total body iron stores. However, large and rapid changes in [FERR] could not have been a reflection of changes in total body iron stores. Equilibrium between [FERR] and total body iron stores could have been temporarily altered by the effects of training. Moreover, iron stores did not seem to have been sufficiently depleted to restrict erythropoiesis. The MCV increased slightly in response to intense training suggesting that training enhances the proportion of young erythrocytes.     

Analysis of the mechanism of change in amplitude of the receptor potential of pacinian corpuscles in Ca++-Deficient solution

The causes of the rise in amplitude of the receptor potential (RP) of Pacinian corpuscles in Ca⁺⁺-free solution were investigated by the external perfusion method. In Ca⁺⁺-free solution the amplitude of RP was shown to increase, but this increase was blocked by the addition of 10–20 mM tetraethylammonium to the solution. A temporary increase in the amplitude of RP was observed in solution with 0.2 mM 2,4-dinitrophenol. The sensitivity of the receptor membrane to mechanical stimuli was unchanged in Ca⁺⁺-free solution. It is suggested that there are no negative charges near the mechanically sensitive ionic channel of the receptor membrane of Pacinian corpuscles which could affect the state of the gating system of the mechanically sensitive channel.Laboratory of General Physiology of Reception, I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR, V. N. Chernigovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 12, pp. 643–645, December, 1979.     

Distribution of ferritin in the rat hippocampus after kainate-induced neuronal injury

A gradual increase in iron occurs in the lesioned hippocampus after neuronal injury induced by the excitotoxin kainate, and the present study was carried out to investigate whether this increase in iron might be associated with changes in expression of the iron binding protein, ferritin. An increase in ferritin immunoreactivity was observed in glial cells of the hippocampus, as early as three days after intracerebroventricular injections of kainate. The number of ferritin positive cells peaked four weeks after the kainate injection, and decreased eight and twelve weeks after injection. They were found to be mostly microglia and oligodendrocytes by double immunofluorescence labeling with glial markers. A number of ferritin-labeled endothelial cells were also observed via electron microscopy. The decline in ferritin immunoreactivity four weeks after the injection of kainate is accompanied by an increase in the number of ferric and ferrous iron positive cells in the lesioned tissue. A substantial non-overlap between ferritin and iron-containing cells was observed. In particular, spherical ferric or ferrous iron-laden cells in the degenerating hippocampus were unlabeled for ferritin for long time periods after the kainate injection. An increase in iron, together with a reduced expression of iron binding proteins such as ferritin at long time intervals after kainate lesions, could result in a relative decrease in ferritin-induced ferroxidase activity and the presence of some of the iron in the ferrous form. It is postulated that this may contribute to chronic neuronal injury, following acute kainate-induced neurodegeneration.     

Excessive iron storage in a patient with Wilson's disease

We report on an otherwise healthy female, mother of two children, with severe decompensated liver cirrhosis due to an iron overload and Wilson's disease. The patient was considered heterozygote for hemochromatosis on the basis of the autosomal recessive inheritance for hemochromatosis, the frequency of the hemochromatosis gene, and the laboratory parameters defining her iron overload. The case is interesting because of the coincidence of Wilson's disease and excessive iron storage. Correspondence to: D. Haussinger     

Sodium conductance in calcium channels of guinea-pig ventricular cells induced by removal of external calcium ions

An inward current characterized by a slow inactivation, was induced when the extracellular Ca^2– concentration was reduced by EGTA. It was suppressed by replacing external Na^– with Tris⁺ or by D-600, increased by epinephrine, and was not affected by TTX. These findings suggest that this current is carried by Na⁺ ions through the Ca channels. The Na current decreased in amplitude as the concentration of external divalent cations was elevated. Blocking the Na current by divalent cations could be approximated by a bimolecular interaction between divalent cation and channel, with a dissociation constant of 1.2 M for Ca²⁺ and 60 M for Mg²⁺. Single channel currents were recorded in the cell-attached configuration. With a pipette solution of pCa=7.5 or pCa>8, the single channel I-V relationship was linear and the slope conductance was 70–75 pS. For 40 mV depolarizations from the resting potential, unitary currents were smaller at pCa=6 than at pCa=7.5. However, single channel events, which were observed after the repolarizing step to the resting potential, were much the same amplitude. The open time histogram was fitted with a single exponential having a time constant of 1.9 ms at around –40 mV (pCa>8, with 5 M Bay K 8644 in the bath solution), which was decreased with increasing the Ca²⁺ concentration in the pipette solution. Noise power spectra of patch currents at pCa=6 revealed a high-frequency component at around 1500 Hz. These results suggest that Ca binding to the sites with a high affinity for Ca²⁺ blocks the Na conductance in Ca channels. Reduction of the unitary current at higher concentrations of Ca²⁺ might be attributed to a rapid block by Ca²⁺.     

Effect of an increased calcium ion concentration on electrical and contractile activity of the smooth muscles of the guinea pig ureter

Smooth muscle cells of the guinea pig ureter were studied by the double sucrose gap method. An increase in the calcium ion concentration in the Ringer-Locke solution to 22 mM led to hyperpolarization and to a slight increase in the resistance of the membrane. The amplitude of the first spike potential and the height of the plateau were lowered but the amplitude of the oscillations was increased. In sodium-free Ringer-Locke solution, when the action potential in the smooth muscle cells of the ureter was converted into a simple spike potential, a marked increase in amplitude of the action potential was observed with an increase in the calcium ion concentration.Department of Neuromuscular Physiology, A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Gorev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 5, pp. 522–526, May, 1977.