Acta Physiologica Scandinavica

Abstract Electroporation designates the use of short high‐voltage pulses to overcome the barrier of the cell membrane. By applying an external electric field, which just surpasses the capacitance of the cell membrane, transient and reversible breakdown of the membrane can be induced. This transient, permeabilized state can be used to load cells with a variety of different molecules, either through simple diffusion in the case of small molecules, or through electrophoretically driven processes allowing passage through the destabilized membrane – as is the case for DNA transfer. Initially developed for gene transfer, electroporation is now in use for delivery of a large variety of molecules: From ions to drugs, dyes, tracers, antibodies, and oligonucleotides to RNA and DNA. Electroporation has proven useful both in vitro, in vivo and in patients, where drug delivery to malignant tumours has been performed. Whereas initial electroporation procedures caused considerable cell damage, developments over the past decades have led to sophistication of equipment and optimization of protocols. The electroporation procedures used in many laboratories could be optimized with limited effort. This review (i) outlines the theory of electroporation, (ii) discusses factors of importance for optimization of electroporation protocols for mammalian cells, (iii) addresses particular concerns when using electroporation in vivo, e.g. effects on blood flow and considerations regarding choice of electrodes, (iv) describes DNA electrotransfer with emphasis on use in the in vivo setting, and (v) sums up data on safety and efficacy of electroporation used to enhance delivery of chemotherapy to tumours in cancer patients.

J. Gehl

Electroporation: theory and methods, perspectives for drug delivery, gene therapy and research

电穿孔：理论与方法，药物递送、基因治疗与研究的前景

Near‐infrared spectroscopy (NIRS) is a non‐invasive method for monitoring oxygen availability and utilization by the tissues. In intact skeletal muscle, NIRS allows semi‐quantitative measurements of haemoglobin plus myoglobin oxygenation (tissue O 2 stores) and the haemoglobin volume. Specialized algorithms allow assessment of the oxidation–reduction (redox) state of the copper moiety (CuA) of mitochondrial cytochrome c oxidase and, with the use of specific tracers, accurate assessment of regional blood flow. NIRS has demonstrated utility for monitoring changes in muscle oxygenation and blood flow during submaximal and maximal exercise and under pathophysiological conditions including cardiovascular disease and sepsis. During work, the extent to which skeletal muscles deoxygenate varies according to the type of muscle, type of exercise and blood flow response. In some instances, a strong concordance is demonstrated between the fall in O 2 stores with incremental work and a decrease in CuA oxidation state. Under some pathological conditions, however, the changes in O 2 stores and redox state may diverge substantially.

R. Boushel

C.A. Piantadosi

Near‐infrared spectroscopy for monitoring muscle oxygenation

近红外光谱法监测肌肉氧合

13 male subjects were studied and placed in 3 groups. Each group exercised one leg with sprint (S), or endurance (E) training and the other leg oppositely or not at all (NT). Oxygen uptake (Vo2), heart rate and blood lactate were measured for each leg separately and for both legs together during submaximal and maximal bicycle work before and after 4 weeks of training with 4-5 sessions per week. Muscle samples were obtained from the quadriceps muscle and assayed for succinate dehydrogenase (SDH) activity, and stained for myofibrillar ATPase. In addition, eight of the subjects performed after the training two-legged exercise at 70% Vo2 max for one hour. The measurements included muscle glycogen and lactate concentrations of the two legs as well as the blood flow and the a-v difference for O2, glucose and lactate.

B. Saltin

Kristina Nazar

D. L. Costill

E. Stein

Eva Jansson

Birgitta Essén

P. D. Gollnick

The Nature of the Training Response; Peripheral and Central Adaptations to One‐Legged Exercise

训练反应的本质：单腿运动的外周和中枢适应

The fatiguability of the quadriceps muscle was investigated in 10 male subjects (25-40 yrs), with inter-individual differences in fibre composition of their vastus lateralis muscles (range 25-65% fast twitch, FT, muscle fibres). Fatiguability was assessed as the decline in maximal force (in % of initial values) with 50 repeated isokinetic knee-extensions at fast angular velocity (3.14 rad/s). Each contraction lasted 0.5 s and the rest periods were about 0.7 s. Every subject was tested on two occasions and the standard deviation for a single determination of fatiguability was 1.4%. The decline in force after 50 contractions was on the average about 45%. The individual values varied, however, and a linear correlation was present between fatiguability and % FT fibres (r = 0.86, p less than 0.01). It was concluded that development of fatigue in human skeletal muscle performing repeated fast dynamic contractions with maximal effort was most marked in muscles with a high proportion FT fibres. This finding was in conformity with earlier results from animal skeletal muscle preparations.

Alf Thorstensson

Jan Karlsson

Fatiguability and Fibre Composition of Human Skeletal Muscle

人类骨骼肌的疲劳性和纤维成分

Abstract Anaerobic performance characteristics of the whole body and at muscle tissue level were studied in 89 athletes and 31 reference subjects. The main parameters were vertical velocity during running up the stairs, maximal isometric force of leg extensor muscles, blood lactate concentration after maximal treadmill running test, percentage of fast twitch muscle fibers (% FT fibers), lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) activity in vastus lateralis muscle. These parameters tended to divide the athletes and their sport events into neuromuscular, anaerobic and aerobic types. The specific needs of the different sport events might have masked the expected characteristics of energy and power utilization. However, a high percentage of FT fibers might be a prerequisite for a successful athlete in certain neuromuscular‐anaerobic type events (“power events”). The main parameters describing the anaerobic performance capacity of the whole body (vertical velocity, leg force, blood lactate) were found to be related to muscle fiber composition (% FT fibers). The running velocity rather than muscle strength seemed to be more influenced by activity of enzymes LDH and CPK.

Paavo V. Komi

Heikki Rusko

Jan Vos

Veikko Vihko

Anaerobic Performance Capacity in Athletes

运动员的无氧运动能力

Abstract Aims: We investigated the ion channel regulation of the resting membrane potential of hair cells with the aim to determine if the resting membrane potential is poised close to instability and thereby a potential cause of the spontaneous afferent spike activity. Methods: The ionic mechanism and the dynamic properties of the resting membrane potential were examined with the whole‐cell patch clamp technique in dissociated saccular hair cells and in a mathematical model including all identified ion channels. Results: In hair cells showing I / V curves with a low membrane conductance flanked by large inward and outward rectifying potassium conductances, the inward rectifier ( K IR ), the delayed outward rectifier ( K V ) and the large conductance, calcium‐sensitive, voltage‐gated potassium channel (BK Ca ) were all activated at rest. Under current clamp conditions, the outward current through these channels balanced the inward current through mechano‐electrical transduction (MET) and Ca 2+ channels. In 45% (22/49) of the cells, the membrane potential fluctuated spontaneously between two voltage levels determined by the voltage extent of the low membrane conductance range. These fluctuations were not influenced by blocking the MET channels but could be reversibly stopped by increasing [K + ] o or by blocking of K IR channels. Blocking the BK Ca channels induced regular voltage oscillations. Conclusions: Two intrinsic dynamical instabilities of V m are present in hair cells. One of these is observed as spontaneous voltage fluctuations by currents through K IR , K V and h ‐channels in combination with a steady current through MET channels. The other instability shows as regenerative voltage changes involving Ca 2+ and K V channels. The BK Ca channels prevent the spontaneous voltage fluctuations from activating the regenerative system.

F. Jørgensen

A. B. A. Kroese

Ion channel regulation of the dynamical instability of the resting membrane potential in saccular hair cells of the green frog (Rana esculenta)

绿蛙（Rana esculenta）囊状毛细胞静息膜电位动态不稳定的离子通道调控

Abstract Aim: In order to identify bacterial compounds which directly affect granulosa cell steroidogenesis, the effect of culture‐supernatants and extracts from Escherichia coli were tested in an in vitro granulosa cell culture model. Methods: Samples were drawn from the culture‐supernatant of E. coli ATCC25922 cultured in Luria‐broth medium. Bacterial extract was prepared by incubation of freshly harvested bacteria in buffer. The bacterial culture‐supernatants and extracts were added to human granulosa cells in culture. The granulosa cells collected from the follicular aspirates from women undergoing in‐vitro fertilization were cultured for 17–53 h and progesterone or oestradiol was assayed in the spent culture medium. Results: The E. coli culture‐supernatant stimulated the basal granulosa cell progesterone production demonstrating its maximum activity reached after 200–240 min of bacterial growth. The heat denaturated bacterial extract as well as its low‐molecular‐weight fraction (&lt;10 kDa) stimulated both the basal and the hCG‐stimulated progesterone production; the oestradiol production was slightly inhibited. Stimulation of progesterone production was time dependent increasing from 125 ± 18% of control within the first 3 h to 205 ± 35% within 17–53 h. The high‐molecular‐weight fraction (&gt;30 kDa) of the bacterial extract inhibited progesterone production. The inhibitory activity was significantly diminished by heat denaturation. Conclusions: The present study demonstrates the existence of various compounds which are secreted by E. coli and could also be extracted out of E. coli bacteria. These bacterial compounds modulate ovarian steroidogenesis. Further studies are needed to clarify how far these compounds contribute to menstrual disturbance observed in chronic pelvic inflammation.

J. Reinsberg

S. Christoffel

A. Kumar

H. van der Ven

Escherichia coli derived factors modulate human granulosa cell steroidogenesis

大肠杆菌衍生因子调节人卵泡颗粒细胞类固醇生成

The activation of both protein kinases A (PKA) and protein kinases C (PKC) in some cell types increases and in others reduces active Na+ efflux. These effects have been ascribed to either a change in the rate of ionic translocation by a fixed number of Na+ pumps or, a change in the number of plasma membrane pumps. The purpose of the present experiments was to study the effect of activating PKA and PKC on the Na+ extrusion by the Na+ pump in frog skeletal muscle.Na+ (22Na+) fluxes and ouabain (3H-ouabain) binding were measured in frog sartorius muscles.Both activation of PKA and PKC increased the active Na+ extrusion by a factor of two; these effects were not additive. Ouabain binding experiments indicated that the pump stimulation by activation of these kinases is not associated with any significant increase in the number of plasma membrane pumps. Stimulation of the active Na+ efflux by protein kinase activation (no change in the number of sarcolemmal pumps) and by hypotonicity (increase in the number of pumps) could be elicited in the same preparation and they were additive.It is concluded that in frog skeletal muscle fibres, (1) activation of both PKA and PKC stimulate the Na+ pump by increasing its rate of ionic translocation; and (2) two modes of Na+ active transport (with and without an increase in the number of pumps) are operative, and can be at work simultaneously, a phenomenon to be reckoned with.

R A Venosa

Protein kinases A and C stimulate the Na+ active transport in frog skeletal muscle without an appreciable change in the number of sarcolemmal Na+ pumps

蛋白激酶A和C刺激蛙骨骼肌中钠离子的主动转运，而肌膜钠泵数量无明显变化

‘Of the 3,800 genes analyzed in the microarray analyses, a total of 75 relevant genes (upregulation of 33 genes and down regulation of 42 genes) displayed alterations with training’ The reasons that pathologic hypertrophy of the left ventricle (LV) (because of hypertension, valvular defects, etc.) is associated with reduced cardiac function, while physiologic or functional LV hypertrophy (induced by exercise training) does not, is a long standing dilemma in cardiovascular biology. Iemitsu et al. used microarray analysis to examine expression levels of 3800 genes in the LV of sedentary and exercise-trained (8 weeks) rats. Results revealed that 75 genes displayed an altered expression pattern 48 h after the last exercise training bout. They selected three of these genes (endothelin-1, glycogen synthase kinase, and calcineurin-inhibitor) and confirmed altered expression with real-time quantitative PCR, Western blots and immunoassay to confirm differential gene expression at the protein and peptide levels. Expression of brain natriuretic peptide (BNP), angiotensin converting enzyme (ACE), and vascular cell adhesion molecule (VCAM-1) in the LV were not altered by exercise but each of these genes has been shown before to exhibit increased expression in pathological LV hypertrophy. These results provide potentially important hints of genes whose expression in LV hypertrophy may partly explain the different clinical and functional outcomes between physiologic and pathologic LV hypertrophy. Thus, this paper serves as an example of how microarrays can be used to screen large numbers of differentially expressed genes in different forms of hypertrophy. These results represent a good first step.

Maurice H. Laughlin

Cardiac gene expression profiling may reveal key differences between physiologic and pathologic cardiac hypertrophy

心脏基因表达谱分析可能揭示生理性和病理性心脏肥大的关键差异

Abstract Aim: The present study was performed to test the hypothesis that the interstitial glucose concentration in human skeletal muscle is decreased for a prolonged period following a single bout of exercise, while blood flow has returned to resting levels. Methods: Muscle interstitial concentrations of glucose, lactate, pyruvate and urea were monitored in six healthy individuals during 8 h following a 2‐h one‐leg exercise session by microdialysis at low perfusion flow rate. Simultaneously the blood flow was measured by the microdialysis ethanol technique. Results: The blood glucose and the control leg interstitial glucose concentrations were stable during the experiment averaging 5.7 ± 0.1 and 4.1 ± 0.3 m m , respectively. In contrast, the interstitial glucose concentration in the exercise leg was markedly decreased, averaging 1.9 ± 0.5 m m , during the first 5.5 h following exercise ( P &lt; 0.01), after which it returned towards normal values. Muscle blood flow at the site of the microdialysis catheter, measured as the ethanol outflow‐to‐inflow ratio, did not change significantly over time in the control or exercise leg and did not differ significantly between the two legs. Interstitial concentrations of lactate, pyruvate and urea were not significantly different between the control and exercise leg. Conclusion: The study shows that the interstitial glucose concentration in skeletal muscle is markedly decreased for several hours following a single exercise session. The decreased interstitial glucose concentration may serve to limit the rate of post‐exercise muscle glucose uptake to a rate compatible with normal blood glucose levels and may also be speculated to have a positive long‐term health implication by augmenting muscle insulin sensitivity.

J. Henriksson

M. Knol

A single bout of exercise is followed by a prolonged decrease in the interstitial glucose concentration in skeletal muscle

一次运动后骨骼肌间质葡萄糖浓度长时间下降

Publication Information	Publisher: John Wiley and Sons Ltd，Publishing cycle: ，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 1940，Proportion of original research papers: ，Self Citation Rate:， Gold OA Rate:

Acta Physiologica Scandinavica

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