Patterns of K/N ratios with growth of guinea pig, beagle, and pig

The influence of age on patterns of K/N ratios (mEq/g) for fat-free whole body organs and tissues was analyzed for the guinea pig, ages 1 to 80 days (82 to 849 g); for the pig, 0 to 89 days (151 to 33,650); and for the beagle, 0 to 383 days (252 to 13,065 g). Strong correlations existed between total K, total N, and fat-free wet weight (FFWW). Mean whole body K/N ratios were 2.57 +/- 0.241 for guinea pigs, 2.53 +/- 0.50 for pigs, and 1.79 +/- 0.27 for beagles. Increase in body weight of the beagle and of the components, skeletal muscle and nonmuscle (whole animal minus skeletal muscle), were divisible into two statistically significant periods: the first from 0 to 62 days, the second from 63 to 383 days. For the first period, the K/N ratio for the whole animal was 1.70 +/- 0.33, for nonmuscle was 1.61 +/- 0.34, and for skeletal muscle was 2.08 +/- 0.50; for the second period, the values were 1.93 +/- 0.22, 1.25 +/- 0.18, and 2.82 +/- 0.83, respectively. Mean K/N ratios of organs and tissues of the pig and beagle differed significantly from mean whole body K/N ratios, with the exception of liver for the beagle and miscellaneous for the pig. Patterns of K/N ratios during increases in FFWW were species-specific for total body as well as for various tissues and organs. As FFWW increased, the whole body K/N ratio did not change significantly in the guinea pig, but decreased significantly in the pig because of the decreased ratio for skeletal muscle. As FFWW of the beagle increased in the first growth period, the slope for the whole body K/N ratio did not differ statistically from zero, although the mean measured ratio increased significantly for liver and skeletal muscle. This increase was counter-balanced by a statistically significant decrease in ratios for skin and skeleton. FFWW continued to increase in the second growth period and the whole body K/N ratio increased, primarily the result of significantly increased ratios for liver and skeletal muscle.(ABSTRACT TRUNCATED AT 400 WORDS)     

Growth of the pig: changes in body weight and body fluid compartments.

Body weight and the rate of change in TBW, ECW, and ICW were measured in 252 anesthetized pigs during the first 12 weeks after birth. After TBW was measured with 3H2O, 55 of the pigs were killed and TBW measured by desiccation. 3H2O overestimated TBW by 6.5% of body weight and 4.9% of fat-free wet weight, compared to desiccation (P less than 0.001); mean figures for 3H2O were 78.6 +/- 1.02% of body weight, and for desiccation, 72.1 +/- 0.45%; on a FFWW basis, 88.6 +/- 0.94% for 3H2O, and 83.7 +/- 0.13% for desiccation. TBW decreased significantly from 85.0% of body weight at birth (1.5 dg) to 75% at 5 kg (day 28) at a rate of ---3.2% body wt/kg body wt (P less than 0.001 from a zero rate). After that the rate of decrease was not different from zero: --0.117% body wt/kg body wt. ECW decreased significantly from 48% at birth to 35% at day 28 at a rate of --3.802% body wt/kg body wt (P less than 0.001 from a zero rate), and after day 28 the rate of decrease was not different from zero (--0.149% body wt/kg body wt) through week 12. ICW decreased, but not significantly, at a rate of --0.099% body wt/kg body wt. The changes in the rate of decrease in TBW and ECW coincided with weaning, and it was speculated that there was a direct relationship between the two events.     

Dynamics and consequences of potassium shifts in skeletal muscle and heart during exercise

Since it became clear that K(+) shifts with exercise are extensive and can cause more than a doubling of the extracellular [K(+)] ([K(+)](s)) as reviewed here, it has been suggested that these shifts may cause fatigue through the effect on muscle excitability and action potentials (AP). The cause of the K(+) shifts is a transient or long-lasting mismatch between outward repolarizing K(+) currents and K(+) influx carried by the Na(+)-K(+) pump. Several factors modify the effect of raised [K(+)](s) during exercise on membrane potential (E(m)) and force production. 1) Membrane conductance to K(+) is variable and controlled by various K(+) channels. Low relative K(+) conductance will reduce the contribution of [K(+)](s) to the E(m). In addition, high Cl(-) conductance may stabilize the E(m) during brief periods of large K(+) shifts. 2) The Na(+)-K(+) pump contributes with a hyperpolarizing current. 3) Cell swelling accompanies muscle contractions especially in fast-twitch muscle, although little in the heart. This will contribute considerably to the lowering of intracellular [K(+)] ([K(+)](c)) and will attenuate the exercise-induced rise of intracellular [Na(+)] ([Na(+)](c)). 4) The rise of [Na(+)](c) is sufficient to activate the Na(+)-K(+) pump to completely compensate increased K(+) release in the heart, yet not in skeletal muscle. In skeletal muscle there is strong evidence for control of pump activity not only through hormones, but through a hitherto unidentified mechanism. 5) Ionic shifts within the skeletal muscle t tubules and in the heart in extracellular clefts may markedly affect excitation-contraction coupling. 6) Age and state of training together with nutritional state modify muscle K(+) content and the abundance of Na(+)-K(+) pumps. We conclude that despite modifying factors coming into play during muscle activity, the K(+) shifts with high-intensity exercise may contribute substantially to fatigue in skeletal muscle, whereas in the heart, except during ischemia, the K(+) balance is controlled much more effectively.     

Stretch receptor-associated expression of alpha 3 isoform of the Na+, K+-ATPase in rat peripheral nervous system

Expression of the neuronal alpha(3) isoform of the Na(+),K(+)-ATPase (alpha(3) Na(+),K(+)-ATPase) was studied in the rat peripheral nervous system using histological and immunohistochemical techniques. Non-uniform expression of the alpha(3) Na(+),K(+)-ATPase was observed in L5 ventral and dorsal roots, dorsal root ganglion, sciatic nerve and its branches into skeletal muscle. The alpha(3) Na(+),K(+)-ATPase was not detected in nerve fibers in skin, saphenous and sural nerves. In dorsal root ganglion 12+/-2% of neurons were immunopositive for alpha(3) Na(+),K(+)-ATPase and all these neurons were large primary afferents that were not labeled by Griffonia simplicifolia isolectin B4 (marker of small primary sensory neurons). In dorsal and ventral roots 27+/-3% and 40+/-3%, respectively, of myelinated axons displayed immunoreactivity for alpha(3) Na(+),K(+)-ATPase. In contrast to the dorsal roots, strong immunoreactivity in ventral roots was observed only in myelinated axons of small caliber, presumably gamma-efferents. In the mixed sciatic nerve alpha(3) Na(+),K(+)-ATPase was detected in 26+/-5% of myelinated axons (both small and large caliber). In extensor hallicus proprius and lumbricales hind limb muscles alpha(3) Na(+),K(+)-ATPase was detected in some intramuscular axons and axonal terminals on intrafusal muscle fibers in the spindle equatorial and polar regions (regions of afferent and efferent innervation of the muscle stretch receptor, respectively). No alpha(3) Na(+),K(+)-ATPase was found in association with innervation of extrafusal muscle fibers or in tendon-muscle fusion regions. These data demonstrate non-uniform expression of the alpha(3) isoform of the Na(+),K(+)-ATPase in rat peripheral nervous system and suggest that alpha(3) Na(+),K(+)-ATPase is specifically expressed in afferent and efferent axons innervating skeletal muscle stretch receptors.     

Bio-impedance analysis for estimation of total body potassium,total body water,and fat-free mass in white,black, and Asian adults

Bio-impedance analysis (BIA) measurements have been used to predict components of body composition. Their validation is required for populations varying in race, sex, and age. In 371 Whites, 182 Blacks and 225 Asians, single-frequency BIA at 50 kHz (RJL-100) resistance and reactance measurements were correlated with same-day measurements of total body water (TBW) by THO dilution, total body potassium (TBK) by whole body ⁴⁰K counting, and fat-free mass (FFM) by dual-photon absorptiometry. BIA correlation coefficients with TBW, TBK, FFM, and fat varied by sex and race for all measured body composition components. The highest correlation was for FFM, and the lowest was for fat mass. Prediction equations were further improved by including age, stature, and weight for each of the study cohorts. The SEE for predictions were in the ranges of 5–6, 6–8, and 7–10% of measured FFM, TBW, and TBK, respectively. BIA was effective in predicting body composition when subjects are specified by age, sex, stature, weight, and race for subjects from 18 to 94 years of age. © 1995 Wiley-Liss, Inc.     

The effect of Na, K and Cl ions on the resting membrane potential of sino-atrial node cell of the rabbit

The resting membrane potential of S-A node cell was investigated by observing the response of the membrane potential to change in [K+]O or [Cl-]O under the presence or absence of Na ion. The slope of the change in membrane potential per decade change in [K+]O increased from 12.3 to 44 mV by removal of Na ion from the external medium, suggesting an extensive contribution of Na ion to the resting membrane potential. To determine the relative conductance between Na and K ions, Cl ion in Tyrode solution was substituted with SCN ion, which is 2.1 times more permeable than Cl ion, in order to eliminate the contribution of Cl concentration cell to the resting membrane potential. The contribution of the Cl ion to the resting membrane potential could be examined only in Na-free medium. Acetate ion has been reported to be 0.5 times less permeable than Cl ion. The replacement of Cl ion by acetate ion in various proportions caused a transient depolarization. The slope of this transient depolarization per decade change of [Cl-]O between 10 to 100 mM was determined to be -6.8mV. Under the assumption that the resting membrane potential could be determined by the parallel concnetration cells for Na, K and Cl, relative conductance ratio between K, Na and Cl was calculated to be 1:0.58:0.15.     

大连地区成年男性身体成分、骨密度、血糖和血脂相关关系

目的:探讨身体成分与骨密度、血糖、血脂的相关性。方法:选择大连地区的汉族成年男性共113名,采用生物电阻抗法分析身体成分,超声骨密度测量仪检测骨密度(BMD),生化分析仪测定血糖(BG)和血脂,计算各项目的平均值及各项目间的相关系数。结果:体脂肪百分数与体质量、体质量指数(BMI)、体脂肪质量和甘油三酯(TG)呈正相关,与高密度脂蛋白胆固醇(HDL-C)呈负相关;BG与体质量、BMI、身体水分(TBW)含量、蛋白质质量、骨骼肌质量、无机盐含量、体脂肪质量、腰臀脂肪比(WHR)和基础代谢率(BMR)呈正相关,与HDL-C和BMD呈负相关;总胆固醇与TG和高、低密度脂蛋白胆固醇呈正相关;TG与年龄、身高、骨骼肌质量、BG和BMD无相关性,与HDL-C呈负相关外,与其他项目均呈正相关;超声波速度、骨折风险指数和骨强度与身高、体质量、BMI、TBW含量、蛋白质质量、无机盐含量、骨骼肌质量、体脂肪质量、WHR、BMR和BG呈正相关。结论:身体成分与BMD、BG、TG和HDL-C具有相关性,与总胆固醇无相关性。     

宫内发育迟缓大鼠胰腺肝脏骨骼肌中胰岛素受体底物的表达

目的分析宫内发育迟缓（IUGR）大鼠胰腺、肝脏、骨骼肌中胰岛素受体底物1（IRS-1）和2（IRS-2）mRNA和蛋白水平的表达,探讨IUGR个体发生胰岛素抵抗的机制。方法采用母孕期低蛋白饮食法建立IUGR大鼠模型,以模型鼠产下的仔鼠为IUGR组;以孕期予正常饮食母鼠产下的仔鼠为对照组。应用RT-PCR法检测各组仔鼠在出生后0、3和8周时点胰腺、肝脏和骨骼肌中IRS-1、IRS-2 mRNA表达水平,采用Western blot检测IRS-1和IRS-2蛋白表达水平。检测3和8周时点仔鼠空腹血糖和血清胰岛素水平,计算胰岛素抵抗指数。结果①IUGR组出生后0和3周体重显著低于对照组;8周时点IUGR组体重显著高于对照组。②IUGR组出生后0、3和8周时点胰腺、肝脏IRS-2 mRNA和蛋白表达水平低于对照组;IRS-1 mRNA和蛋白表达水平与对照组差异无统计学意义;骨骼肌IRS-1 mRNA和蛋白表达水平均显著低于对照组;IRS-2蛋白表达水平与对照组差异无统计学意义。③至8周时点,骨骼肌IRS-1 mRNA和蛋白表达水平的下降幅度较胰腺和肝脏组织更为明显;肝脏IRS-2 mRNA和蛋白表达水平的下降幅度较胰腺和骨骼肌组织更为明显。④至8周时点,IUGR组空腹血糖水平与对照组差异无统计学意义,胰岛素水平和空腹胰岛素抵抗指数较对照组显著升高。结论 IUGR大鼠胰腺、肝脏和骨骼肌组织均存在IRS-1或IRS-2 mRNA和蛋白表达水平的下降,可能是发生胰岛素抵抗的机制之一。     

Cellular Cl content and concentration of amphibian skeletal and heart muscle.

Toads (Bufo marinus) and frogs (Rana pipiens pipiens) were given intraperitoneal injections of Na36Cl and Na235SO4. After in vivo equilibration for 20--180 min, the animals were pithed, and their ventricular and semitendinosus muscles were excised. Measurements of total Cl (by titrimetry) and 36Cl (by radioassay) showed that specific radioactivities of plasma and mus les approached equality within 1 h after injection for toad skeletal and heart muscle and frog ventricles, indicating complete exchange of cellular Cl with 36Cl. From the simultaneously measured muscle water contents and 35SO4 spaces, intracellular Cl concentrations in vivo (in mumol/g cell water) for semitendinosus and ventricular muscles were calculated to be, respectively, 1.4 +/- 0.3 and 2.3 +/- 0.8 for Bufo and 1.7 +/- 0.7 and 4.8 +/- 2.4 for Rana. In view of these low values, active cellular Cl accumulation seems improbable, but cannot be rigorously excluded without simultaneous membrane potential and intracellular ion activity measurements. A high concentration of Cl in the sarcoplasmic reticulum of skeletal muscle is also inconsistent with these measurements.     

Effects of ouabain,age and K-depletion on K-uptake in rat soleus muscle

The relationship between the number of³H-ouabain binding sites and the Na, K-pump mediated K-uptake has been characterized in rat soleus muscle. By brief exposure to³H-ouabain (1×10^–6–1×10^–5mol/l) in vitro, it could be measured that 19–94% of the ouabain binding sites had been occupied. This was associated with a proportionate decrease in the ouabain suppressible K-uptake indicating that under strictly standardized conditions, measurements of³H-ouabain binding sites quantify functional Na,K-pumps.When 3 week old rats were K-depleted for a further week followed by K-repletion 2 h before measurements, the³H-ouabain binding site concentration was 61% lower than in age-matched control soleus muscles. However, the ouabain suppressible K-uptake was only reduced by 35% partly because intracellular Na remained higher in the muscles obtained from K-depleted rats.From the 1st to the 4th week of life, the³H-ouabain binding site concentration increased 2.9-fold. In contrast, the ouabain suppressible K-uptake decreased by a factor 3.5. Accordingly, in muscles from 1 week old rats, the ouabain suppressible K-uptake per³H-ouabain binding site was 10-fold higher than in muscles from 4 week old rats. This difference could not be accounted for by changes in intracellular Na, total or extracellular water. It may be related to differentiation and change in structure.On the basis of the present results and those reported in the literature for mouse and frog skeletal muscle it was calculated that under resting conditions at 30°C in vitro, isolated skeletal muscles only utilize between 3 and 25% of their total capacity for active Na, K-transport. Therefore, variations in the total Na, K-pump capacity may not readily be detected in measurements of the ouabain suppressible rate of K-uptake.     

Body water compartments with human aging using fat-free mass as the reference standard.

Forty-five healthy men and women aged 16-39 and 59-89 yr were studied for total body water (TBW) and extracellular water (ECW); intracellular water (ICW) was calculated as the difference (ICW = TBW - ECW). An independent measurement of total body fat by inert gas uptake provided a value (+/- 2%) for fat-free mass (FFB is wt minus body fat). Results agreed with observations by others that TBW and ICW are lower in the aged and lower in women, whether expressed as absolute volumes or per unit of weight, surface area, or height. However, with FFB as the reference standard very different aging trends appeared. TBW/FFB remained constant to our oldest measured subjects (704 +/- 7 ml/kg). ICW/FFB was slightly lower at advanced age, but the 4-5% decrease for each sex was within statistical variability. With age ECW increased slightly and its proportion within the fat-free body (ECW/FFB) was significantly higher. Based upon FFB, the distribution, proportions, and aging trends of body water compartments were similar for men, women, and male rats. Although its potential limitations must be appreciated, the FFB appears widely useful as a reference standard. The stability of ICW volume and of fat-free mass in aging man does not support the hypothesis that cellular mass is lost by healthy mammals with age.     

Transport of electrolytes across the helicoidal colon of the new-born pig.

1. The Na, K, Cl and water content of faeces removed from different parts of the pig helicoidal colon were determined for 1-day-old and adult animals. Faecal Na, Cl and water content fell in both cases during passage of contents through the colon. K content increased in the distal colon of the adult pig. This did not occur in the 1-day-old animal. 2. The colon of the 1-day-old pig removed a larger proportion of water from its contents than did that of the adult. The absorption of both water and Cl was found to extend into the distal colon of the 1-day-old animal; little or no net absorption took place in this region in the adult. 3. Colons taken from new-born pigs maintained stable short-circuit currents of about 60-80 muA cm-2 with open-circuit voltages of about 10 mV. Similar values were found for proximal and mid regions of colons taken from 1-day-old, suckled animals. In the distal colon, however, both short-circuit current and open-circuit potential doubled after suckling. 4. Measurements of Na flux in vitro showed no regional difference at birth. The amount of Na absorbed, about 4.5 muequiv cm-2 h-1, was twice that predicted from the short-circuit current, supposing that to be due solely to the electrogenic transport of Na. 5. Colons taken from suckled pigs transported Na at double the rate found in the new-born animal. This applied to both the proximal region, where the short-circuit current remained constant, and the distal region, where the short-circuit was double that of the new-born. 6. Fluxes of Cl and K were also measured across the proximal colon of the one-day-old, suckled pig. There was a net absorption of Cl and secretion of K (1.3 and -0.05 muequiv cm-2 h-1 respectively). These fluxes, taken together with that for Na, could not wholly account for the short-circuit current measured across these preparations. 7. The pig colon seems well able to cope with both electrolyte and water absorption during the first 24 hr of post-natal life. Part of the absorbed sodium appears to follow a non-electrogenic, possibly pinocytotic, route, but the full ionic contribution to the measured short circuit current has still to be determined.     

Effects of removal of Na(+) and Cl(-) on spontaneous electrical activity, slow wave, in the circular muscle of the guinea-pig gastric antrum

In the circular muscle of the guinea-pig gastric antrum, a decrease in the external Na(+) to less than 20 mM produced depolarization of the membrane with transient prolongation of the slow wave. This was followed by a high rhythmic activity. The activity was inhibited by reapplication of Na(+) before recovery. The depolarization in Na(+)-deficient solution was prevented and rhythmic activity continued at about 5/min for at least 6 min by simultaneous removal of K(+), Ca(2+), or Cl(-). After exposure to a Na(+)- and Cl(-)-deficient solution for a few minutes, reapplication of the Na(+) in Cl(-)-deficient solution inhibited generation of the slow wave until Cl(-) reapplication. Similar results were obtained when Na(+) and Cl(-) were reapplied in the absence of K(+) after exposure to a Na(+)-, K(+)-free, and Cl(-)-deficient solution, although the inhibition was weaker than Na(+) reapplication in a Cl(-)-deficient solution. In the presence of furosemide or bumetanide, a strong inhibition of activity was produced by the reapplication of Na(+) and Cl(-) after exposure to an Na(+)- and Cl(-)-deficient solution. A hypothesis is presented that intracellular Ca(2+) concentration ([Ca(2+)](i)) is the most important factor determining the generation and frequency of the slow wave and that [Ca(2+)](i) is regulated by the Na(+) concentration gradient across the plasma membrane. The recovery of the Na(+) concentration gradient by Na(+) reapplication after removal of Na(+) and Cl(-) is mainly controlled by a Na(+)-K(+)-Cl(-) co-transport.     

Changes in element composition of A6 cells following hypotonic stress

Cellular element concentrations and dry weight contents were determined in A6 epithelia using electron microprobe analysis. This was done to assess the quantitative contributions of Na, K and Cl to the regulatory volume decrease (RVD) and isovolumetric regulation (IVR) after decreasing the basolateral osmolality from 260 to 140 mosmol/kg in a stepwise or gradual way. Two minutes after inducing acute hypotonic stress the cells behaved almost like ideal osmometers, as indicated by a pronounced increase in cell height and decreases in the cellular dry weight and concentrations of all measured elements by about the same degree. Sixty minutes after inducing acute hypotonic stress the dry weight and concentrations of the impermeant elements P, Mg and Ca had returned approximately to control values, indicating normalized cell volume. Na, K and Cl concentrations, however, remained greatly reduced. The cellular amounts of Na, K and Cl diminished during RVD by approximately 31%, 24% and 46%, respectively. The dry weights and element concentrations measured 60 min after inducing acute hypotonic stress were similar to those obtained after a continuous reduction of basolateral osmolality. The cellular loss of Na and K following hypotonic stress exceeded that of Cl by about 40 mmol/kg wet wt., suggesting the exit of an other anion and/or the titration of fixed negative charges. The contribution of Na, K and Cl to total cellular osmolality increased from about 75% under control conditions to about 85% during RVD and IVR. Since only approximately 70% of the loss of cellular osmolytes necessary for the observed RVD and IVR is accounted for by the cellular exit of Na, K and Cl, other osmolytes, possibly amino acids, must leave the cells following hypotonic stress.     

Effect of K-depletion on 3H-ouabain binding and Na-K-contents in mammalian skeletal muscle

K-depletion induced by K-deficient fodder led to hypokalemia, decreased K-content and increased Na-content in skeletal muscle of rats. The heart showed similar, although more modest changes, whereas brain, erythrocytes and liver maintained virtually constant Na-K-contents. K-depletion decreased total binding capacity for 3H-ouabain by up to 76%, an effect which could be demonstrated both in vitro and in vivo. Following 3 weeks of K-depletion, the apparent KD for 3H-ouabain binding to rat soleus was 1.3 X 10(-7) M as compared to 2.4 X 10(-7) M in controls. Also in mice and guinea pigs, K-depletion induced a selective loss of K from muscle and decreased 3H-ouabain binding capacity. K-depletion induced by diuretics or fluorohydrocortisone gave similar effects. The effects of K-depletion on 3H-ouabain binding capacity were confirmed by measurements of 3-O-methylfluorescein phosphatase activity, an enzyme activity which is closely correlated to the Na-K-ATPase activity. Following readministration of K, the K-contents of plasma and muscle reached control levels in 24 hours, but 3H-ouabain binding capacity was not normalized until after 6 days of K-repletion. In mammalian skeletal muscle, K-depletion leads to a marked and reversible reduction in 3H-ouabain binding capacity, which may be secondary to the selective loss of K or gain of Na.     

Muscle growth and fiber type composition in hind limb muscles during postnatal development in pigs

Rapid postnatal development in pigs is reflected by differentiation in skeletal muscle. This process depends on muscle function and demands, but a comprehensive overview of individual developmental characteristics of quickly growing leg muscles in pigs is still missing. This study focused on the development of 10 hind limb muscles in pigs. To determine these changes in mass, fiber type patterns and fiber diameters were analyzed 0, 2, 4, 7, 14, 28, 42, 56 and 400 days after birth. Generally, the proportion of slow fibers increased from birth to 8 weeks. Thereafter, only minor changes in muscle fiber type composition were observed. The majority of the muscles contained less then 10% slow-twitch fibers at birth, increasing to between 12 (Musculus vastus lateralis) and 38% (M. gastrocnemius medialis) in adult pigs. By contrast, postural muscles already had 20-30% slow fibers at birth, and this contribution increased up to 65% in adults (i.e. M. vastus intermedius). From birth to the 2nd week, only in slow fibers could activity of oxidative enzymes be detected. A differentiation of fast-twitch fibers into subtypes with high (comparable to type IIA) and low oxidative metabolism (equivalent to type IIB) occurred between the 2nd and 4th week of life. The ratio between type II fibers with high and low oxidative enzyme activity did not change markedly through development in any muscle, although there was a trend towards an increasing proportion of type IIA fibers in the soleus. In the majority of the muscles investigated, the fast-twitch fibers with low oxidative metabolism (IIB) obtained the largest cross-sectional area. In contrast, at birth no remarkable differences in the diameter of fast and slow fibers were found. The rapid increase in muscle mass compared to body mass reflects the high performance in meat production of the cross pig investigated.     

CI-ATPase and Na+/K(+)-ATPase activities in Alzheimer's disease brains

The enzyme activities and the protein levels of Cl(-)-ATPase and Na+/K(+)-ATPase were examined in Alzheimer's disease (AD) brains. Cl(-)-ATPase and Na+/K(+)-ATPase activities in AD brains (n = 13) were significantly lower than those in age-matched control brains (n = 12). In contrast, there was no significant difference in anion-insensitive Mg2(+)-ATPase activity between the two groups. Western blot analysis revealed that the protein levels of Cl(-)-ATPase, Na+/K(+)-ATPase and neuron specific Na+/K(+)-ATPase alpha3 isoform were also significantly reduced in AD brains, while the amount of protein disulfide isomerase, one of the house keeping membrane proteins, was not different between the two groups. The data first demonstrated that Cl(-)-ATPase and Na+/K(+)-ATPase are selectively impaired in AD brains, which may reduce the gradients of Na(+), K(+) and Cl(-) across the cell membranes to cause excitotoxic cellular response and the resulting neuronal death.     

Protein synthesis and RNA in tissues of the pig.

The rate of protein synthesis in 75-kg pigs was measured by continuous intravenous infusion of [14C]tyrosine. In the whole body, over 600 g of protein were synthesized each day. In pigs, rats, and man the rate of protein synthesis in the whole body was related to metabolic rate. The fractional rate of synthesis of protein in the tissues was also measured. The proteins of visceral organs (liver kidney, lung, and spleen) were renewed at rates close to 20% per day, those of brain at 8% per day, heart 7% per day, and skeletal muscle 4% per day. A significant correlation was observed between the fractional rate of protein synthesis in the tissue and RNA concentration. Calculation of the total amount of protein synthesized in skeletal muscle of the pig (fractional rate of synthesis X protein content) shows that muscle contributes 42% of whole-body synthesis. By contrast, in the rat only 19% of whole-body synthesis occurs in muscle.