Skeletal Muscle Potassium Research Articles

Potassium in skeletal muscle in untreated primary hypertension and in chronic renal failure, studied by X-ray fluorescence technique.

Muscle biopsy specimens form 22 patients with primary hypertension, 10 patients with chronic renal failure and 21 healthy normotensive controls were analyzed using a Kevex 0600 X-ray spectrometer. Muscle potassium (MK), calcium (MCa), sulphur (MS) and phosphorus (MP) were determined. In the patients with primary hypertension, MK was decreased compared to the controls (p less than 0.001), MCa was increased (p less than 0.05), MS was decreased (p less than 0.05) and no difference was seen in MP. In the patients with chronic renal failure, MK was decreased compared to the controls (p less than 0.001), MCa showed no difference compared to the controls, whereas both MP and MS were lower (p less than 0.05 and p less than 0.001). It was concluded that intracellular potassium is low both in primary hypertension and chronic renal failure. In chronic renal failure the potassium decrease is probably secondary to loss of cellular potassium capacity, whereas in primary hypertension an inhibition of the sodium, potassium, adenosine triphosphatase is suggested as the cause of the low potassium.

Muscle electrolyte measurements during and after hypokinesia in determining muscle electrolyte depletion during hypokinesia in the rat.

Hypokinesia (diminished movement) induces muscle mineral depletion. However, the mechanism of muscle mineral depletion during hypokinesia (HK) remains unknown. Measuring electrolyte retention and electrolyte values in muscle, plasma, and urine during and after HK, the aim of this study was to discover if HK could depress mineral retention and lead to muscle mineral depletion. Studies were done on 204 13-wk-old male Wistar rats (370-390 g) during 10 d pre-HK period, 98 d HK period, and 15 d post-HK period. Rats were equally divided into two groups: vivarium control rats (VCR) and hypokinetic rats (HKR). All hypokinetic rats were kept for 98 d in small individual cages, which restricted their movements in all directions without hindering food and water intakes. All control rats were housed for 98 d in individual cages under vivarium control conditions. Both groups of rats were pair-fed. During the HK period skeletal muscle sodium (Na), potassium (K), magnesium (Mg), calcium (Ca), and water content and electrolyte retention decreased significantly (p < 0.05), while urinary and plasma electrolyte levels increased significantly (p < 0.05) in HKR compared with their pre-HK values and their respective VCR. During the initial days of the post-HK period, mineral retention increased significantly (p < 0.05), plasma and urinary electrolyte level decreased significantly (p < 0.05), while muscle electrolyte and water content remained significantly (p < 0.05) depressed in HKR compared with VCR. Muscle mineral and water content, electrolyte retention, plasma, and urinary electrolyte values did not change in VCR compared with their pre-HK values. It was concluded that during HK decreased muscle mineral content may suggest muscle mineral depletion, while increased urinary electrolyte loss and muscle mineral depletion may demonstrate reduced mineral retention. Reduced electrolyte excretion and depressed muscle mineral content during post-HK may indicate skeletal muscle mineral depletion during HK. Dissociation between electrolyte retention and muscle mineral depletion may demonstrate the presence of decreased electrolyte retention as the mechanism of muscle electrolyte depletion during prolonged HK.

K+ transport in resting rat hind-limb skeletal muscle in response to paraxanthine, a caffeine metabolite

This study tested the hypothesis that paraxanthine, a caffeine metabolite, stimulates skeletal muscle potassium (K+) transport by an increase in Na+ -K+ ATPase activity. The unidirectional transport of K+ into muscle (J(in)K) was studied using a perfused rat hind limb technique. Using 12 hind limbs, we examined the response to 20 min of paraxanthine perfusion (0.1 mM), followed by 20 min perfusion with 0.1 mM paraxanthine and 5 mM ouabain (n = 5) to irreversibly inhibit Na+ -K+ ATPase activity. Paraxanthine stimulated J(in)K by 23+/-5% within 20 min. Ouabain abolished the paraxanthine-induced stimulation of J(in)K, suggesting the increase in K+ uptake was due to activation of the Na+ -K+ ATPase. To confirm the role of the Na+ -K+ ATPase, 14 hind limbs were perfused for 20 min with 5 mM ouabain prior to 20 min perfusion with 0.1 mM paraxanthine and 5 mM ouabain (n = 6). Ouabain alone resulted in a 41+/-7% decrease in J(in)K within 15 min. Inhibition of ouabain-sensitive J(in)K prevented the paraxanthine-induced increase in J(in)K. Hind limbs (n = 3) were also perfused with 0.1 mM paraxanthine for 60 min to examine the response to longer duration paraxanthine perfusion. The paraxanthine-induced increase in J(in)K continued for the entire 60 min. In another series, hind limbs were perfused with 0.01 (n = 9), 0.1 (n = 9), or 0.5 (n = 6) mM paraxanthine for 15 min. There was no concentration-dependent relationship between J(in)K and paraxanthine concentration, and 0.01, 0.1, and 0.5 mM paraxanthine increased J(in)K similarly (25+/-5, 22+/-4, and 27+/-6%, respectively). The effect of paraxanthine on J(in)K could not be reversed by subsequent perfusion with paraxanthine-free perfusate. Caffeine (0.05-1.0 mM) had no effect on K+ transport. It is concluded that paraxanthine increases J(in)K in resting skeletal muscle by stimulating ouabain-sensitive Na+ -K+ ATPase activity.

Skeletal muscle magnesium and potassium by gender and hypertensive status

The relation between blood pressure and skeletal muscle magnesium and potassium, and the relation between these electrolytes and body mass index, blood lipids, blood glucose and plasma insulin concentrations were studied in 29 hypertensive and 21 normotensive men. In addition, a comparison was made between the normotensive men and 37 normotensive women regarding the concentrations of muscle potassium and magnesium. Mean skeletal muscle potassium concentration was lower and plasma insulin higher in hypertensives compared to normotensives. Systolic and diastolic blood pressures were inversely correlated to muscle potassium and positively correlated to insulin. Muscle magnesium was positively correlated to muscle potassium but not to blood pressure. Muscle magnesium was significantly higher in normotensive women, compared to normotensive men. Muscle potassium did not differ between the genders.

Magnesium Substitution and Postoperative Arrhythmias in Patients Undergoing Coronary Artery Bypass Grafting

Sixty coronary artery bypass grafting patients were randomized to receive either magnesium sulphate or placebo for 4 days postoperatively. The magnesium substitution reduced the duration of atrial fibrillation or flutter (p < 0.05), but not the number of patients developing these arrhythmias. The number of ventricular ectopic beats was also reduced among patients receiving magnesium sulphate compared to placebo (p < 0.05). To evaluate whether the anti-arrhythmic effect of magnesium sulphate was explained by a faster resumption of cellular potassium postoperatively, skeletal muscle electrolyte concentrations were measured pre-operatively and on the third day postoperatively. No significant difference was found in skeletal muscle potassium or magnesium contents on the third day postoperatively when comparing the two groups. The serum magnesium level declined postoperatively in the placebo group, whereas an increase was found in patients receiving magnesium sulphate. We suggest magnesium substitution as a routine postoperatively, because this treatment seems to reduce the severity of postoperative arrhythmias.

Effects of training on potassium, calcium and hydrogen ion regulation in skeletal muscle and blood during exercise

Ionic regulation is critical to muscle excitation, contraction and metabolism, and thus for muscle function during exercise. This review focuses on the effects of training upon K+, Ca2+ and H+ ion regulation in muscle and K+ regulation in blood during exercise. Training enhances K+ regulation in muscle and blood and reduces muscular fatiguability. Endurance, sprint and strength training in humans induce an increased muscle Na+, K+ pump concentration, usually associated with a reduced rise in plasma [K+] during exercise. Although impaired muscle Ca2+ regulation plays a vital role in fatigue, little is known about possible training effects. In rat fast-twitch muscle, overload-induced hypertrophy and endurance training were associated with reduced sarcoplasmic reticulum Ca2+ uptake, consistent with fast-to-slow fibre transition. In human muscle, endurance and strength training had no effect on muscle Ca2+ ATPase concentration. Whilst muscle Ca2+ uptake, release and Ca2+ ATPase activity were depressed by fatigue, no differences were found between strength athletes and untrained individuals. Muscle H+ accumulation may contribute to fatigue during intense exercise and is also modified by sprint training. Sprint training may increase muscle Lac- and work output with exhaustive exercise, but the rise in muscle [H+] is unchanged or attenuated, indicating a reduced rise in muscle [H+] relative to work performed. Muscle buffering capacity can be dissociated from this improved H+ regulatory capacity after training. Thus, training enhances muscle and blood K+ and muscle H+ regulation during exercise, consistent with improved muscular performance and reduced fatiguability; however, little is known about training effects on muscle Ca2+ regulation during contraction.

Postoperative arrhythmias and myocardial electrolytes in patients undergoing coronary artery bypass grafting.

Electrolyte changes in right atrial and skeletal muscle pre- intra- and postoperatively, and their relationship to the development of postoperative atrial fibrillation or flutter were evaluated in 31 patients with coronary artery bypass grafting (CABG). Such postoperative arrhythmias occurred in 14 patients (45%). Before CABG the skeletal muscle potassium concentration was lower in these patients than in the others: median 261.4 (range 148.2-329.5) vs 298.6 (167.1-416.4) mumol/g dry weight, p = 0.017. The right atrial potassium concentration was normal, but sodium levels were higher in the patients with, than in those without postoperative arrhythmias: median 340.3 (263.7-454.9) vs 296.3 (203.9-355.0) mumol/g dry weight, p = 0.008, indicating disturbed transmembrane electrolyte transfer. During CABG the potassium levels fell and sodium increased in both right atrium and skeletal muscle, and on postoperative day 2 the potassium content in skeletal muscle was not yet restored. Magnesium levels showed no changes in right atrium or skeletal muscle, but serum magnesium declined postoperatively. As the observed electrolyte derangements may be important in the development of postoperative arrhythmias, concomitant potassium and magnesium supplement postoperatively may be beneficial in restoring cellular potassium concentration.

86Rb is not a reliable tracer for potassium in skeletal muscle

For technical reasons, 86Rb is frequently preferred to 42K as a tracer for K+. Systematic comparisons of the two isotopes, however, are rarely done. In this paper we compare the transport of 42K and 86Rb in rat and mouse soleus muscle and in rat erythrocytes. Ouabain-suppressible K+ uptake in rat soleus was the same whether measured with 42K or 86Rb, both when stimulated by insulin, salbutamol and calcitonin-gene-related peptide (CGRP), and when inhibited by graded concentrations of ouabain. Control experiments with rat erythrocytes, where Na(+)-K(+)-Cl- co-transport has earlier been demonstrated, showed closely similar inhibitory effects of bumetanide on 42K and 86Rb uptake. In contrast, bumetanide produced no significant change in 42K uptake of rat and mouse soleus muscle, but clearly inhibited 86Rb uptake at concentrations down to 10(-7) M (P < 0.001). Whereas the addition of 150 mM NaCl had no effect on 42K uptake in rat soleus, 86Rb uptake, and in particular the bumetanide-suppressible component, was markedly increased by this addition. The inhibitory effect of bumetanide on 86Rb uptake gives rise to the false impression that skeletal muscle contains a NaKCl2 co-transport system. Efflux studies showed that the fractional loss of 42K from rat soleus muscle is 2.3 times larger than that of 86Rb. Salbutamol and CGRP increased 86Rb efflux, but inhibited 42K efflux. This implies that for studies of K+ efflux and bumetanide-sensitive K+ transport, 86Rb is not even an acceptable tracer for the detection of qualitative changes. Control experiments with 42K are essential in any characterization of unknown K+ transport processes.

Skeletal muscle sodium and potassium changes after successful surgery in acromegaly: relation to body composition, blood glucose, plasma insulin and blood pressure

The aim of this study was to investigate the skeletal muscle sodium/potassium (Na/K) ratio in acromegaly before and 1 year after trans-sphenoidal removal of a growth hormone (GH)-secreting pituitary adenoma. Muscle biopsies were taken and skeletal muscle electrolytes, body composition, glucose, insulin and blood pressure were studied. Fasting blood glucose and plasma insulin levels, but not blood pressure, were higher in acromegalic patients (N = 9) than in controls (N = 6). The skeletal muscle potassium content was higher (p < 0.01) but the sodium content and the Na/K ratio were lower (p < 0.05 and p < 0.001, respectively) in untreated patients with acromegaly as compared to weight-matched healthy controls. Elevated GH, glucose and insulin levels normalized after surgery. Blood pressure remained unchanged. The total body potassium content, the lean body mass and the total body water content decreased and the body fat content increased while the body weight was unchanged. The skeletal muscle potassium content decreased from [medium (range)] 9.8 (9.2-11.5) to 7.7 (5.7-9.5) mmol/100 g wet wt (p < 0.001). The skeletal muscle sodium content increased from 2.8 (2.5-3.9) to 5.1 (4.3-6.7) mmol/100 g wet wt (p < 0.001) and the Na/K ratio increased from 0.28 (0.26-0.38) to 0.56 (0.51-1.18) (p < 0.001) after surgery, which is a higher level than the controls with a Na/K ratio of 0.47 (0.39-0.84) (p < 0.01). These changes seem to be mediated by a decreased GH effect on the Na/K pump after successful trans-sphenoidal surgery in acromegaly.

Electrochemical potentials of potassium in skeletal muscle under different metabolic states.

Intracellular potassium and membrane potential were measured simultaneously by means of double-barrelled liquid ion-exchange microelectrodes in single fibers of rat thigh muscle in vivo in rats maintained in seven different metabolic states. The K+ equilibrium potential (EK) was more negative than the simultaneously measured membrane potential (Em) in the normal state by 18.4 mV. K+ loading, acute and chronic, resulted in depolarization of Em due to increased serum K+ (hyperkalemia) with no increase in intracellular K+. K+ depletion resulted in hyperpolarization of Em as plasma K+ decreased proportionately more than intracellular K+. Low Na+ diet had no effect. Intracellular K+ was decreased in acute acidosis but not in the chronic state. Thus K+ depletion and acute acidosis are associated with intracellular K+ decrease. The fact that hyperpolarization exists in the former and not the latter is a reflection that hypokalemia accompanies the former condition. The hyperpolarizing states of K+ depletion and chronic acidosis are accompanied by decreased excitability and muscle weakness.

Skeletal muscle depressed calcium and phosphofructokinase in chronic heart failure are upregulated by captopril ‐ a double‐blind, placebo‐controlled study

The effects of the angiotensin converting enzyme inhibitor captopril, after treatment for 5-6 weeks with 25 mg t.i.d., were studied in 12 patients with stable moderate heart failure. Five patients received placebo treatment, and the two groups were comparable at baseline. Angiotensin II levels decreased in response to captopril therapy. Skeletal muscle potassium, magnesium and chloride levels did not differ from reference values. Calcium was subnormal (P less than 0.0001), but increased to the reference range during captopril treatment. Phosphofructokinase, a rate-limiting glycolytic enzyme, was in the lower reference range and increased (P less than 0.04) in response to captopril therapy. In conclusion, stable moderate heart failure is associated with low levels of skeletal muscle calcium and phosphofructokinase activity, these metabolic changes tending to return to normal levels with captopril treatment.

Total body potassium, skeletal muscle potassium and magnesium in patients with Bartter's syndrome

In 20 patients with Bartter's syndrome, who had a serum potassium concentration of 2.75 +/- 0.29 mmol/l (mean +/- SD), the total body potassium (TBK) was measured and compared with a predicted value obtained from regression equations based on age, sex, body height and weight. A significant difference was found between the observed and predicted TBK (mean -320 +/- 306 mmol, p less than 0.01). A positive correlation existed between the serum potassium concentration and the ratio observed TBK/predicted TBK. However, the average fractional reduction in TBK (-11%) was less than the average fractional decrease in serum potassium concentration (-32%). Muscle biopsy specimens were obtained from four patients with Bartter's syndrome and 10 control subjects for analyses of potassium and magnesium. The serum concentrations of potassium and magnesium were decreased in these patients. The potassium content in muscle tissue was lower in two of four patients, but no difference in the amount of magnesium was observed.

Sequence of a human fetal skeletal muscle potassium channel cDNA related to RCK4

Sequence of a human fetal skeletal muscle potassium channel cDNA related to RCK4

Skeletal muscle potassium increases after diet and weight reduction in obese subjects with normal and impaired glucose tolerance.

Body composition calculated from total body potassium and skeletal muscle potassium were studied in middle-aged obese men and women with normal and impaired glucose tolerance as well as Type II diabetes before and after advice on calorie reduction during twelve months. The subjects were compared with healthy lean men and women. Mean weight loss was 6.6 kg (P less than 0.05). Lean body mass and body fat decreased 2.0 kg (P less than 0.05) and 4.6 kg (P less than 0.05), respectively. Total body potassium decreased by a mean of 146 +/- 49 mmol (P less than 0.01). Obese men with Type II diabetes and impaired glucose tolerance had lower total body potassium and muscle potassium levels than obese healthy men. After dieting, the obese men and women increased their muscle potassium levels with a mean of 2.8 mmol/100 fat-free dry weight to 42.6 +/- 2.6 mmol/100 g fat-free dry weight (P less than 0.05), but they were still below the levels of the lean controls, 44.4 +/- 1.3 MMOL/100 g fat-free dry weight, (P less than 0.01). Increase in skeletal muscle potassium was correlated to decrease in body weight, r = 0.55 (P less than 0.01) and to decrease in fasting blood glucose, r = 0.42 (P less than 0.05).

Increased skeletal muscle Na/K-ratio in obese men, but not in women, with glucose intolerance.

Obesity is associated with glucose intolerance. Glucose is to a large extent disposed in the skeletal muscle. Peripheral insulin resistance, as well as decreased enzymatic activity in the skeletal muscle, has been suggested in type II diabetes. Potassium is essential for such enzymatic reactions. In this study, obese men, but not women, with glucose intolerance tended to have a lower total body potassium per kg body weight, indicating a smaller muscle mass, than weight-matched normoglycaemic men. They also had a lower skeletal muscle potassium content per 100 g dry weight (P less than 0.05) and a higher muscle Na/K-ratio (P less than 0.05) compared with obese men with normal glucose tolerance. Muscle fat and muscle sodium content were higher in obese men than in women with the same body mass index (P less than 0.01). The muscle electrolyte changes can be explained by a decrease in the insulin mediated Na/k-pump activity across the cell membrane or a smaller number of insulin receptors on the skeletal muscle cell in patients with glucose intolerance.

Reduced concentrations of potassium, magnesium, and sodium-potassium pumps in human skeletal muscle during treatment with diuretics

Animal studies have shown that potassium depletion induced by diuretics or potassium deficient fodder leads to a selective decrease in the concentrations of potassium and in the concentration of sodium-potassium pumps in skeletal muscle. In 25 patients who had received diuretics for 2-14 years the mean concentrations of potassium, magnesium, and sodium-potassium pumps were measured in skeletal muscle biopsy specimens and were significantly lower than in those from a group of age matched controls. The reductions in all three variables were significant in those patients receiving diuretics for arterial hypertension as well as in those being treated for congestive heart failure. In 14 patients the mean muscle potassium concentration was below the control range, but only one of those was hypokalaemic (3.4 mmol/l), and 13 were receiving potassium supplements. In 15 patients the mean muscle magnesium concentration was below normal, and the mean muscle potassium and magnesium concentrations showed a linear correlation. In 12 patients in whom the mean muscle potassium concentration was below 80 mumol/g wet weight there was a linear correlation between the cellular potassium:sodium ratio and the concentration of 3H-ouabain binding sites indicating that potassium deficiency also leads to a down regulation of sodium-potassium pumps in human skeletal muscle. In spite of potassium supplements long term treatment with diuretics may lead to potassium and magnesium deficiencies, which are not detectable using the standard methods of serum analysis. The changes in concentrations of electrolytes and sodium-potassium pumps associated with treatment with diuretics may impair muscle function and potassium homoeostasis and interfere with the distribution of digitalis glycosides.

Magnesium, potassium and zinc deficiency in subjects with type II diabetes mellitus.

The concentrations of magnesium, potassium and zinc were determined in plasma, erythrocytes, muscle biopsies, and in urine collected during 24 hours, in 18 subjects with type II diabetes mellitus (DM). Magnesium was also determined in mononuclear cells. The results were compared with those in 35 (magnesium and potassium analyses) or 26 (zinc analyses) healthy controls. Subjects with type II DM had lower concentrations of magnesium (3.79 +/- 0.32 vs. 4.29 +/- 0.22 mmol/100 g FFDS), potassium (40.5 +/- 5.17 vs. 46.1 +/- 3.81 mmol/100 g FFDS) and zinc (231 +/- 29 vs. 247 +/- 23 ng/mg FFDS) in skeletal muscle. Furthermore, the urinary excretions of magnesium and zinc were higher, as compared with those in healthy controls (5.00 +/- 2.68 vs. 3.62 +/- 1.47 mmol/24 hours, and 683 +/- 285 vs. 326 +/- 205 micrograms/24 hours, respectively). The contents of magnesium, potassium and zinc plasma did not correlate with the corresponding concentrations in skeletal muscle or circulating blood cells, as investigated in healthy controls, diabetics and in all subjects together, implying that the plasma concentrations are not useful in the assessment of electrolyte status. Hence, deficiency of electrolytes frequently occurs, and should be looked for, in subjects with type II DM.

Decreased skeletal muscle potassium in obesity.

The effect of body weight on total body potassium, skeletal muscle electrolytes and fat content was studied in seven lean and seven obese middle-aged men and seven lean and eight obese middle-aged women. Total body potassium and total body fat increased with body weight (p less than 0.01 and less than 0.05 for men, and p less than 0.05 and p less than 0.001 for women, respectively). So did muscle fat in men (p less than 0.01), while muscle tissue potassium was decreased in both obese men (p less than 0.001) and obese women (p less than 0.05). The skeletal muscle Na/K-ratio tended to be higher in obese men (p less than 0.1) but was not related to body weight in women. Skeletal muscle magnesium was higher (p less than 0.01) in obese men than in lean men. No differences between lean and obese women were found. Obese men had higher diastolic blood pressure (p less than 0.05) than lean men, while there was no difference between obese and lean women. Compared with lean subjects, obese subjects thus had lower relative skeletal muscle mass and men, especially, had more fat and less potassium in the skeletal muscle.

Effects of triamterene on serum and skeletal muscle electrolytes in diuretic-treated patients.

The effects on plasma and skeletal muscle electrolytes of the combination of triamterene 37.5 mg and hydrochlorothiazide 25 mg daily were studied in 19 patients on prior long-term (greater than 1 year) diuretic therapy for arterial hypertension and/or congestive heart failure. A further 20 patients fulfilling the same admission criteria were used as controls. Blood samples and skeletal muscle biopsies were taken before the study and after 6 months on therapy. The diuretic-treated group had a significant increase in skeletal muscle potassium and magnesium after 6 months on therapy as compared to the controls. Thus, the combination of triamterene and hydrochlorothiazide appeared effective in preserving the cellular content of potassium and magnesium on a long-term basis in the type of patient studied.

Tissue electrolyte changes induced by high doses of diuretics in rats.

High doses of furosemide administered orally to growing rats for 4 weeks induced a pronounced fall in the concentration of magnesium and potassium in plasma, of magnesium in bone and potassium in skeletal muscle, but did not cause any reduction of these ions in the myocardium. The only electrolyte change in the heart of furosemide exposed rats was a higher calcium concentration than in rats of the control group. The addition of amiloride to furosemide in the ratio 1:16 mg corrected and partly overcorrected for the losses of magnesium and potassium in plasma and skeletal muscle. It is concluded that long term amiloride administration prevented magnesium and potassium losses induced by furosemide and that the myocardium was relatively resistant to furosemide induced magnesium and potassium loss.