Drug Modulation of Transductor Function of Na+,K+-ATPase

Experimental proof of the hypothesis on modulation of the transductor function of Na⁺,K⁺-ATPase by the ouabain—Ca²⁺ chelate complex was obtained by the method organotypic tissue culture. Quantum chemical estimations detected two principally different modes of Ca²⁺ ion chelation by ouabain molecule. It is hypothesized that the ouabain—Ca²⁺—Na⁺,K⁺-ATPase ligand-receptor complex is formed due to ion-ion bonds. The formation of the complex serves as the signal triggering the enzyme transductor function. It is experimentally proven that ouabain is incapable of inhibiting neurite growth in sensory neuron and heart tissue explants after removal of free calcium from the nutrient medium with EGTA. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 146, No. 10, pp. 416–418, October, 2008     

Potassium effect on Na+, K+-ATPase activity of cultured newborn rat astroblasts during differentiation

High K⁺ concentration effect on Na⁺, K⁺-ATPase activity of cultured newborn rat astroblasts has been studied in conditions under which astrocytic differentiation could have taken place. In 14-day-old cultures, no potassium effect could be found reflecting the undifferentiated state of these cultures. After dibutyryl-cyclic AMP treatment, which induces a morphological transformation suggesting a differentiation, no K⁺ effect appears but the specific enzyme activities are higher than in control cells reflecting the development of numerous cellular processes. After 28 days of cultivation — a cultivation period which closely corresponds to the time of astrocytic differentiation in vivo — Na⁺,K⁺-ATPase activity at 25 and 50 mM K⁺ concentrations are higher than at 10 mM, suggesting that an astrocytic differentiation has taken place in vitro.     

Melatonin attenuates chronic immobilization stress-induced muscle atrophy in rats: Influence on lactate-to-pyruvate ratios and Na+/K+ ATPase activity

This study assessed the protective effect of melatonin against muscle atrophy provoked by chronic immobilization stress (CIS). CIS was induced in rats by limiting their trunk movement for 90?min daily for 6 weeks. Rats subjected to the CIS procedure demonstrated a substantial decrease in body weight, an increase in serum corticosterone, muscle atrophy, and an increase in atrogin-1 mRNA levels. An increase in the serum lactate-to-pyruvate ratio and the oxidative stress accompanied by a reduction of Na⁺/K⁺ ATPase activity could be responsible for these changes. Melatonin efficiently attenuated CIS-induced deleterious effects on the muscle by reducing corticosterone levels, the lactate-to-pyruvate ratio, and oxidative stress, thereby improving Na⁺/K⁺ ATPase activity and muscle condition. We conclude that melatonin can contribute to the prevention of CIS-induced muscle atrophy via its anti-stress, anti-oxidant properties and its effect on Na⁺/K⁺ ATPase activity.     

Kinetics of Ca2+ Uptake into Lectin-Induced Secondary Lymphocytes during Reactivation with Concanavalin A or Interleukin 2

The kinetics of Ca2+ uptake into lectin-induced secondary lymphocytes was studied during reactivation to DNA synthesis with concanavalin A (Con A) or interleukin 2 (IL-2). IL-2 did not cause any significant uptake of Ca2+ into the lymphocytes, while Con A induced an accumulation of Ca2+ into the lymphocytes which reached a maximum 1 to 2 h after the addition of the lectin. The time during which Ca2+ uptake occurred corresponded to the time of dependence on extracellular Ca2+ for lectin-induced DNA synthesis. The increased rate of Ca2+ accumulation and the shortened Ca2+ dependence period of secondary lymphocytes as compared with primary lymphocytes could explain the ability of secondary lymphocytes to display an accelerated response, in terms of DNA synthesis, to re-stimulus.     

The pharmacology of ATP-sensitive K+ channels in the heart

What is known to date about the pharmacology of ATP-sensitive K⁺ channels has provided evidence that important differences exist between cardiac and pancreatic cells: (i) sulphonylureas are about two orders of magnitude more potent in the pancreas than in the heart; (ii) diazoxide exerts opposite effects in the heart and in the pancreas.Since glibenclamide and potassium channel openers are potent and specific inhibitors and activators of K⁺-ATP channels, they respectively have emerged as powerful tools to assess both the positive or deleterious roles of the channels during cardiac ischemia.     

视网膜神经节细胞凋亡对延迟整流钾电流的影响

目的:观察视网膜神经节细胞(retinal ganglion cells,RGCs)凋亡对延迟整流钾电流(delayed rectifier K~+ currents,I_K)的影响。方法:将原代培养2~3 d的SD乳大鼠RGCs分为对照组、加压0.5 h组、加压1 h组、加压1.5 h组和加压2 h组,对照组为常规培养6 d;其它各组常规培养6 d后用自行设计的加压装置加压80 mmHg,时间分别为0.5 h、1 h、1.5 h和2 h,通过连续波长多功能微孔板检测仪检测各组RGCs线粒体的荧光强度;通过全细胞膜片钳技术观察各组细胞膜电容(membrane capacitance,C_m)的变化,观察对照组与加压1 h组I_K、V_(1/2)、k和G_(max)的变化。结果:对照组RGCs线粒体的荧光强度与加压0.5 h组比较差异无统计学显著性,而加压1 h、1.5 h和2 h各组RGCs线粒体的荧光强度显著低于对照组(P0.05);对照组RGCs的细胞Cm与加压0.5 h组比较差异无统计学显著性,其余各组RGCs的细胞C_m显著低于对照组(P0.05)。与对照组比较,加压1 h能使电流幅度显著增加,在刺激电位为-10 m V~60 m V时,加压1 h组的电流密度明显大于对照组(P0.05)。加压1 h组的G_(max)值明显高于对照组(P0.05),V_(1/2)显著小于对照组(P0.01),两组间比较k值的差异无统计学显著性。结论:视网膜神经节细胞凋亡伴有I_K通道电导增加,I_K增大。     

Clusters of axonal Na+ channels adjacent to remyelinating Schwann cells

Summary Rat sciatic nerve fibres were demyelinated by injection of lysolecithin and examined at several stages as Schwann cells proliferated, adhered, and initiated remyelination. Immunoperoxidase EM has been used to follow the clustering of Na⁺ channels that represents an early step in the formation of new nodes of Ranvier. At the peak of demyelination, 1 week postinjection, only isolated sites, suggestive of the original nodes, were labelled. As Schwann cells adhered and extended processes along the axons, regions of axonal Na⁺ channel immunoreactivity were often found just beyond their leading edges. These channel aggregates were associated only with the axolemma and Na⁺ channels were not detected on glial membranes. Sites with more than one cluster in close proximity and broadly labelled aggregates between Schwann cells suggested that new nodes of Ranvier formed as neighbouring Na⁺ channel groups merged. Schwann cells thus seem to play a major role in ion channel distributions in the axolemma. In all of these stages Na⁺ channel label was found primarily just outside the region of close contact between axon and Schwann cell. This suggests that Schwann cell adherence acts in part to exclude Na⁺ channels, or that diffusible substances are involved and can act some distance from regions of direct contact.     

Expression of CD28 on CD8+ and CD4+ Lymphocytes During HIV Infection

CD28 interaction with B7 molecules, expressed on the membranes of antigen-presenting cells, costimulates cytokine production, T-cell proliferation and generation of cytotoxic lymphocytes. The expression of CD28 markers on CD4⁺ and CD8⁺ lymphocytes was studied in a group of subjects at various stages of HIV infection. A reduction in the percentage of CD28-bearing CD4⁺ and CD8⁺ cell subsets was observed during the asymptomatic stage of the disease. This reduction was more pronounced in AIDS than in non-AIDS patients. At the same time, an increase in the absolute CD8⁺CD28⁻ cell number (greater in stage A than in stage B and C subjects) was observed in HIV-infected patients. The finding of an altered pattern of CD28 expression on T cells might per se explain certain early defects in the cytokine pattern and in the immune response peculiar to HIV-infected patients.     

Apical K+ channels of frog diluting segment: inhibition by acidification

The apical potassium conductance of the amphibian diluting segment is regulated by the intracellular pH. Alkalinisation of the cytosol, whether directly by bathing the cell in an alkaline medium, or following activation of an apical Na/H exchanger by aldosterone, results in an increase in the K conductance.Early distal tubules were isolated from slices of Frog kidneys and the apical membranes exposed by everting the tubule with the aid of microperfusion pipettes. Single channels in the apical membrane were studied in the cell-attached configuration while the tubules were bathed in Ringer with a pH of either 7.4 (control) or 6.6 (acid).Under control conditions single channel currents were readily seen at the resting membrane potential. Upon acidification of the superfusion solution the open probability of the channels was decreased from 0.76 to 0.15. Thus the reduction in apical conductance is brought about, at least in part, by a reduction in the open probability of the channels upon cellular acidification.