Adynamia episodica hereditaria with myotonia: A non-inactivating sodium current and the effect of extracellular pH

To study the mechanism of periodic paralysis, we investigated the properties of intact muscle fibers biopsied from a patient who had adynamia episodica hereditaria with electromyographic signs of myotonia. When the potassium concentration in the extracellular medium, [K]e, was 3.5 mmol/l, force of contraction, membrane resting potential, and intracellular sodium activity were normal, but depolarizing voltage clamp steps revealed the existence of an abnormal inward current. This current was activated at membrane potentials less negative than -80 mV, reached a maximum within 50 msec, and was not inactivated with time. The inward current was completely and reversibly blocked by tetrodotoxin, which indicates that it was carried by sodium ions. In a solution containing 9 mmol/l potassium, normal muscle would depolarize to -63 mV and yet be capable of developing full tetanic force upon stimulation. The muscle from the patient depolarized to -57 mV and became inexcitable, i.e., it was paralyzed. A contracture did not develop. Lowering of the extracellular pH did not influence the resting potential, but it effectively antagonized or prevented the paralytic effect of high [K]e by changing the inactivation characteristics of the sodium channels. Hydrochlorothiazide, which had a therapeutic effect on the patient, did not prevent paralysis in vitro. An abnormal rise of the intracellular sodium activity was recorded when the extracellular potassium concentration was raised to 10 mmol/l

Na+,K+-pump stimulation improves contractility in isolated muscles of mice with hyperkalemic periodic paralysis

In patients with hyperkalemic periodic paralysis (HyperKPP), attacks of muscle weakness or paralysis are triggered by K+ ingestion or rest after exercise. Force can be restored by muscle work or treatment with β2-adrenoceptor agonists. A missense substitution corresponding to a mutation in the skeletal muscle voltage-gated Na+ channel (Nav1.4, Met1592Val) causing human HyperKPP was targeted into the mouse SCN4A gene (mutants). In soleus muscles prepared from these mutant mice, twitch, tetanic force, and endurance were markedly reduced compared with soleus from wild type (WT), reflecting impaired excitability. In mutant soleus, contractility was considerably more sensitive than WT soleus to inhibition by elevated [K+]o. In resting mutant soleus, tetrodotoxin (TTX)-suppressible 22Na uptake and [Na+]i were increased by 470 and 58%, respectively, and membrane potential was depolarized (by 16 mV, P < 0.0001) and repolarized by TTX. Na+,K+ pump–mediated 86Rb uptake was 83% larger than in WT. Salbutamol stimulated 86Rb uptake and reduced [Na+]i both in mutant and WT soleus. Stimulating Na+,K+ pumps with salbutamol restored force in mutant soleus and extensor digitorum longus (EDL). Increasing [Na+]i with monensin also restored force in soleus. In soleus, EDL, and tibialis anterior muscles of mutant mice, the content of Na+,K+ pumps was 28, 62, and 33% higher than in WT, respectively, possibly reflecting the stimulating effect of elevated [Na+]i on the synthesis of Na+,K+ pumps. The results confirm that the functional disorders of skeletal muscles in HyperKPP are secondary to increased Na+ influx and show that contractility can be restored by acute stimulation of the Na+,K+ pumps. Calcitonin gene-related peptide (CGRP) restored force in mutant soleus but caused no detectable increase in 86Rb uptake. Repeated excitation and capsaicin also restored contractility, possibly because of the release of endogenous CGRP from nerve endings in the isolated muscles. These observations may explain how mild exercise helps locally to prevent severe weakness during an attack of HyperKPP

Uncovering the Importance of Selenium in Muscle Disease

A connection between selenium bioavailability and development of muscular disorders both in humans and livestock has been established for a long time. With the development of genomics, the function of several selenoproteins was shown to be involved in muscle activity, including SELENON, which was linked to an inherited form of myopathy. Development of animal models has helped to dissect the physiological dysfunction due to mutation in the SELENON gene; however the molecular activity remains elusive and only recent analysis using both in vivo and in vitro experiment provided hints toward its function in oxidative stress defence and calcium transport control. This review sets out to summarise most recent findings for the importance of selenium in muscle function and the contribution of this information to the design of strategies to cure the diseases

Sociala mediers påverkan på investerares riskbenägenhet : En undersökning av medierande faktorer

Det senaste decenniet har användandet av sociala medier exploderat och blivit en plattformdär information och tips om aktier och investeringar delas ut. Unga personer är de störstaanvändarna av sociala medier, och tidigare studier visar att denna åldersgrupp uppvisar ettmer riskfyllt beteende på aktiemarknaden. Syftet med denna studie var således att undersökahuruvida det finns ett samband mellan aktivitet på sociala medier och riskbenägenhet. Vidareundersöktes om tre variabler - överdrivet självförtroende, ångeraversion och kognitivdissonans - hade en medierande effekt i sambandet mellan aktivitet på sociala medier ochriskbenägenhet. En kvantitativ metod med en enkätstudie användes för studiensdatainsamling. Statistiska mått, däribland regressionsanalys och medieringsanalys, användesför att besvara forskningsfrågan. Resultaten visade att sociala medier har en statistisktsignifikant effekt på riskbenägenhet på aktiemarknaden, och att överdrivet självförtroende haren statistiskt signifikant medierande effekt på relationen. Det fanns inga belägg ellerindikationer på att kognitiv dissonans och ångeraversion har en medierande effekt.Sammanfattningsvis visade studien att aktivitet på sociala medier i investeringssyfte kanbidra till ökad riskbenägenhet, och att överdrivet självförtroende har en viktig roll sommedierande variabel i förhållandet. The last decade, the use of social media has escalated and become a platform whereinformation and tips about stocks and investments are shared. Young individuals aregenerally the most frequent users of social media, and studies also show that the same agegroup displays a more risk-prone behavior in financial markets. Therefore, the purpose of thisstudy was to examine the potential effect of social media activity on risk propensity on thestock market. Furthermore, the study investigated whether the three variables -overconfidence, regret aversion, and cognitive dissonance - could be classified as a mediatingvariable between social media activity and risk propensity. The study was conducted using aquantitative method, employing a survey, where 130 people responded. Statistical measuressuch as regression analysis and mediation analysis were used to answer the research question.The results showed that social media has a statistically significant effect on risk propensity onthe stock market, and that overconfidence has a statistically significant mediating effect onthe relationship. There was no evidence or indication that cognitive dissonance or regretaversion has a mediating effect. In summary, the study demonstrated that use of social mediain investment purposes can increase risk willingness, and that overconfidence plays animportant role as a mediating variable in this relationship.