In skeletal muscle, excitation may cause loss of K+, increased extracellular K+ ([K+]o), intracellular Na+ ([Na+]i), and depolarization. Since these events interfere with excitability, the processes of excitation can be self-limiting. During work, therefore, the impending loss of excitability has to be counterbalanced by prompt restoration of Na+-K+ gradients. Since this is the major function of the Na+-K+ pumps, it is crucial that their activity and capacity are adequate. This is achieved in two ways: 1) by acute activation of the Na+-K+ pumps and 2) by long-term regulation of Na+-K+ pump content or capacity. 1) Depending on frequency of stimulation, excitation may activate up to all of the Na+-K+ pumps available within 10 s, causing up to 22-fold increase in Na+ efflux. Activation of the Na+-K+ pumps by hormones is slower and less pronounced. When muscles are inhibited by high [K+]o or low [Na+]o, acute hormone- or excitation-induced activation of the Na+-K+ pumps can restore excitability and contractile force in 10-20 min. Conversely, inhibition of the Na+-K+ pumps by ouabain leads to progressive loss of contractility and endurance. 2) Na+-K+ pump content is upregulated by training, thyroid hormones, insulin, glucocorticoids, and K+ overload. Downregulation is seen during immobilization, K+ deficiency, hypoxia, heart failure, hypothyroidism, starvation, diabetes, alcoholism, myotonic dystrophy, and McArdle disease. Reduced Na+-K+ pump content leads to loss of contractility and endurance, possibly contributing to the fatigue associated with several of these conditions. Increasing excitation-induced Na+ influx by augmenting the open-time or the content of Na+ channels reduces contractile endurance. Excitability and contractility depend on the ratio between passive Na+-K+ leaks and Na+-K+ pump activity, the passive leaks often playing a dominant role. The Na+-K+ pump is a central target for regulation of Na+-K+ distribution and excitability, essential for second-to-second ongoing maintenance of excitability during work.

Na+-K+ Pump Regulation and Skeletal Muscle Contractility

Exercise limitation in chronic heart failure: Central role of the periphery

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 c...

https://www.physiology.org/doi/pdf/10.1152/physrev.2000.80.4.1411

Dynamics and Consequences of Potassium Shifts in Skeletal Muscle and Heart During Exercise

Stress hormones, adrenaline (epinephrine) and noradrenaline (norepinephrine), are responsible for many adaptations both at rest and during exercise. Since their discovery, thousands of studies have focused on these two catecholamines and their importance in many adaptive processes to different stressors such as exercise, hypoglycaemia, hypoxia and heat exposure, and these studies are now well acknowledged. In fact, since adrenaline and noradrenaline are the main hormones whose concentrations increase markedly during exercise, many researchers have worked on the effect of exercise on these amines and reported 1.5 to >20 times basal concentrations depending on exercise characteristics (e.g. duration and intensity). Similarly, several studies have shown that adrenaline and noradrenaline are involved in cardiovascular and respiratory adjustments and in substrate mobilization and utilization. Thus, many studies have focused on physical training and gender effects on catecholamine response to exercise in an effort to verify if significant differences in catecholamine responses to exercise could be partly responsible for the different performances observed between trained and untrained subjects and/or men and women. In fact, previous studies conducted in men have used different types of exercise to compare trained and untrained subjects in response to exercise at the same absolute or relative intensity. Their results were conflicting for a while. As research progressed, parameters such as age, nutritional and emotional state have been found to influence catecholamine concentrations. As a result, most of the recent studies have taken into account all these parameters. Those studies also used very well trained subjects and/or more intense exercise, which is known to have a greater effect on catecholamine response so that differences between trained and untrained subjects are more likely to appear. Most findings then reported a higher adrenaline response to exercise in endurance-trained compared with untrained subjects in response to intense exercise at the same relative intensity as all-out exercise. This phenomenon is referred to as the 'sports adrenal medulla'. This higher capacity to secrete adrenaline was observed both in response to physical exercise and to other stimuli such as hypoglycaemia and hypoxia. For some authors, this phenomenon can partly explain the higher physical performance observed in trained compared with untrained subjects. More recently, these findings have also been reported in anaerobic-trained subjects in response to supramaximal exercise. In women, studies remain scarce; the results are more conflicting than in men and the physical training type (aerobic or anaerobic) effects on catecholamine response remain to be specified. Conversely, the works undertaken in animals are more unanimous and suggest that physical training can increase the capacity to secrete adrenaline via an increase of the adrenal gland volume and adrenaline content.

Catecholamines and the effects of exercise, training and gender.

During exercise the cardiovascular system has to warrant substrate supply to working muscle. The main function of red blood cells in exercise is the transport of O2 from the lungs to the tissues and the delivery of metabolically produced CO2 to the lungs for expiration. Hemoglobin also contributes to the blood’s buffering capacity, and ATP and NO release from red blood cells contributes to vasodilation and improved blood flow to working muscle. These functions require adequate amounts of red blood cells in circulation. Trained athletes, particularly in endurance sports, have a decreased hematocrit, which is sometimes called “sports anemia”. This is not anemia in a clinical sense because athletes have in fact an increased total mass of red blood cells and hemoglobin in circulation relative to sedentary individuals. The slight decrease in hematocrit by training is brought about by an increased plasma volume. The mechanisms that increase total red blood cell mass by training are not understood fully. Despite stimulated erythropoiesis, exercise can decrease the red blood cell mass by intravascular hemolysis mainly of senescent red blood cells, which is caused by mechanical rupture when red blood cells pass through capillaries in contracting muscles, and by compression of red cells e.g. in foot soles during running or in hand palms in weightlifters. Together, these adjustments cause a decrease in the average age of the population of circulating red blood cells in trained athletes. These younger red cells are characterized by improved oxygen release and deformability, both of which also improve tissue oxygen supply during exercise.

/pdf/red-blood-cells-in-sports-effects-of-exercise-and-training-zqaba4bwbl.pdf

Red blood cells in sports: effects of exercise and training on oxygen supply by red blood cells.

Relations among exercise acidosis and various electrolyte concentrations in plasma of femoral venous blood were investigated during bicycling. At equal work rates the changes in endurance trained athletes were compared with the changes in non-athletes. The increase of [Ca++] and [Mg++] could be explained by hemoconcentration. In untrained [H+], [K+], [orthophosphate] (P
 i
 ), [lactate] (Lac) and [protein] (Prot) increased significantly more than in trained subjects. Actual [HCO3
−] rose at low work rates, at higher rates it decreased in the untrained while remaining constant in the athletes. [Cl−] did not change during work. Na+ shift into the working muscles must occur. A high correlation does exist between [H+] and [K+], [P
 i
 ] and Na+ shift, respectively. This confirms the concept of a strong interaction between the H+ and the Na+−K+ transport. Probably P
 i
 follows K+ through the cell membrane. From the ratio of K+ and P
 i
 release it might be possible to calculate the intracellular pH. The calculated osmolality (Osm) increased more in untrained than in trained subjects primarily caused by changes in [Lac−] and [HCO3
−].

Exercise acidosis as cause of electrolyte changes in femoral venous blood of trained and untrained man

In experiments with graded exercise of 15 men (6 untrained, 3 semitrained, 6 endurance-trained) the trained subjects showed a massive shift to the right of thein vivo O2 dissociation curve (ODC) of femoral venous blood. At a saturation of 20 to 25% (18 mkp/sec)PO2 was about 9 mm Hg higher for the trained than for the untrained group. The following factors play a role: 1. The 2,3-diphosphoglycerate [2,3-DPG] concentration was increased by 15 to 20% in the trained group which explains about 2 mm Hg of the difference inPO2. 2. Exercise acidosis in the femoral venous blood depends to a large extent on CO2 in the trained, but on lactic acid in the untrained group. At low saturations the CO2-Bohr effect increases sharply thus having a greater importance in the trained subjects. This factor can explain about 2 mm Hg of the difference. However, influence of chloride and 2,3-DPG on the Bohr effect must be taken into consideration. 3. Since the large ODC-shift to the right of the trained group was not reproducible underin vitro conditions, it is suggested that a rapidly decaying unknown substance accounts for the remaining difference inPO2.

Influences of exercise and endurance training on the oxygen dissociation curve of blood under in vivo and in vitro conditions.

The relationship of femoral venous [K+], [H+], osmolality (OSM), PO2, and [inorganic phosphate] ([Pi]) with heart rate (HR), ventilation (VE), and calculated leg blood flow (Q) were investigated during bicycle exercise in endurance trained (TR) and untrained (UT) test subjects. At a given VO2 the increases of [K+], OSM, [Pi] and the decrease of PO2 were significantly lower in TR than in UT. In the same proportion the increases of HR, VE, and Q were diminished. Thus in TR and UT identical and highly significantly correlated regression lines of [K+], [H+], OSM, [Pi] and PO2 with HR, VE, and Q were obtained. These constituents changed in the same proportion as the relative VO2 in TR and UT. No relationships with [Na+], [Ca++], and [ Mg++] were found. By means of a multiple regression analysis the partial influence of K+, H+, OSM, PO2, and Pi upon the total change of HR, VE and Q was estimated to compare with data from infusion experiments. The findings were discussed in view of the hypothesis that these candidates may provide linkage between metabolic events, circulatory, and ventilatory adjustments during work.

Relationships of femoral venous [K+], PO2, osmolality, and [orthophosphate) with heart rate, ventilation, and leg blood flow during bicycle exercise in athletes and non-athletes.

To evaluate to what metabolic event in contracting muscles heart rate (HR) and 
$$\dot V$$

 
E are related, time courses of femoral and cubital venous [K+], osmolality (OSM), pH, PCO2, PO2, [lactate], and [orthophosphate] ([Pi]) at onset of exercise were studied in athletes (TR) and non-athletes (UT) and compared to time courses of HR and 
$$\dot V$$

 
E. During ischaemic work with the calf muscles it could be shown that most of these blood constituents were only released from contracting muscles. Thus their time courses reflected the metabolic events in working muscles being not essentially disturbed by non-working parts of the body. Ischaemic work induced, however, substantial increases of HR and 
$$\dot V$$

 
E. In the course of non-ischaemic bicycle work HR and 
$$\dot V$$

 
E rose more rapidly in TR than in UT but were lower in TR during the steady state. During non-ischaemic work only the increases of femoral venous [K+] closely mimicked the cardiorespiratory transients in TR as well as in UT. None of the other femoral venous substances showed such a rapid change or such typical variations between TR and UT. Cubital venous [K+] and [Pi] approached femoral venous concentrations only in the second minute after start whereas pH, PCO2, and OSM increased mainly in venous outflow from contracting muscles. PO2 decreased in femoral venous blood of TR and UT, but in cubital venous blood it remained depressed only in UT. It was discussed that the cardiorespiratory adjustment during the initial stages of work was related to K+ release in working muscles and not to O2 consuming or H+ producing processes, nor to release of Pi or increase of OSM.

Heart rate and ventilation in relation to venous [K+], osmolality, pH, PCO2, PO2, [orthophosphate], and [lactate] at transition from rest to exercise in athletes and non-athletes.

Bernd Hemmer

Papers

Exercise acidosis as cause of electrolyte changes in femoral venous blood of trained and untrained man

Influences of exercise and endurance training on the oxygen dissociation curve of blood under in vivo and in vitro conditions.

Relationships of femoral venous [K+], PO2, osmolality, and [orthophosphate) with heart rate, ventilation, and leg blood flow during bicycle exercise in athletes and non-athletes.

Heart rate and ventilation in relation to venous [K+], osmolality, pH, PCO2, PO2, [orthophosphate], and [lactate] at transition from rest to exercise in athletes and non-athletes.

In vivo and in vitro investigations on the oxygen dissociation curve of blood of trained and untrained subjects during exercise.