Impairment of skeletal muscle adenosine triphosphate-sensitive K+ channels in patients with hypokalemic periodic paralysis.
The adenosine triphosphate (ATP)-sensitive K+ (KATP) channel is the most abundant K+ channel active in the skeletal muscle fibers of humans and animals. In the present work, we demonstrate the involvement of the muscular KATP channel in a skeletal muscle disorder known as hypokalemic periodic paralysis (HOPP), which is caused by mutations of the dihydropyridine receptor of the Ca2+ channel. Muscle biopsies excised from three patients with HOPP carrying the R528H mutation of the dihydropyridine receptor showed a reduced sarcolemma KATP current that was not stimulated by magnesium adenosine diphosphate (MgADP; 50-100 microM) and was partially restored by cromakalim. In contrast, large KATP currents stimulated by MgADP were recorded in the healthy subjects. At channel level, an abnormal KATP channel showing several subconductance states was detected in the patients with HOPP. None of these were surveyed in the healthy subjects. Transitions of the KATP channel between subconductance states were also observed after in vitro incubation of the rat muscle with low-K+ solution. The lack of the sarcolemma KATP current observed in these patients explains the symptoms of the disease, i.e., hypokalemia, depolarization of the fibers, and possibly the paralysis following insulin administration. (+info)
C-terminal HERG mutations: the role of hypokalemia and a KCNQ1-associated mutation in cardiac event occurrence.
BACKGROUND: The long-QT syndrome (LQTS) is a genetically heterogeneous disease in which 4 genes encoding ion-channel subunits have been identified. Most of the mutations have been determined in the transmembrane domains of the cardiac potassium channel genes KCNQ1 and HERG. In this study, we investigated the 3' part of HERG for mutations. METHODS AND RESULTS: New specific primers allowed the amplification of the 3' part of HERG, the identification of 2 missense mutations, S818L and V822 M, in the putative cyclic nucleotide binding domain, and a 1-bp insertion, 3108+1G. Hypokalemia was a triggering factor for torsade de pointes in 2 of the probands of these families. Lastly, in a large family, a maternally inherited G to A transition was found in the splicing donor consensus site of HERG, 2592+1G-A, and a paternally inherited mutation, A341E, was identified in KCNQ1. The 2 more severely affected sisters bore both mutations. CONCLUSIONS: The discovery of mutations in the C-terminal part of HERG emphasizes that this region plays a significant role in cardiac repolarization. Clinical data suggests that these mutations may be less malignant than mutations occurring in the pore region, but they can become clinically significant in cases of hypokalemia. The first description of 2 patients with double heterozygosity associated with a dramatic malignant phenotype implies that genetic analysis of severely affected young patients should include an investigation for >1 mutation in the LQT genes. (+info)
Hypokalemia with syncope caused by habitual drinking of oolong tea.
A 61-year-old woman developed hypokalemia, atrioventricular block and ventricular tachycardia with syncope after habitual drinking 2 to 3 liters of oolong tea per day. She had been suffering from rheumatoid arthritis and Sjogren's syndrome and her serum albumin was decreased (2.9 g/dl). Oolong tea contains caffeine at approximately 20 mg/dl. Great quantities of caffeine can induce hypokalemia. The serum protein binding caffeine is albumin. Accordingly, in patients with hypoalbuminemia, caffeine is apt to induce hypokalemia. This case suggested that great quantities of oolong tea, one of the so-called "healthy" drinks, result in serious symptoms for patients with hypoalbuminemia. (+info)
Early prediction of neurological outcome after falls in children: metabolic and clinical markers.
Falls are the foremost reason for non-fatal injuries and are second only to motor vehicle accidents in causing accidental death. The purpose of this study was to identify the clinical and metabolic predictors of the outcome of head injury caused by falls from a height. Medical records of 61 children who had been admitted to the paediatric intensive care unit from 1990 to 1993 after falling from a height were reviewed retrospectively. Outcomes were categorised as good, moderate, severe, and poor. Glasgow coma scores, pupillary responses, brain oedema, and midline shift are significantly associated with poor outcome (p < 0.05). Metabolic markers associated with poor outcome included hyperglycaemia and hypokalaemia. Children with a poor outcome had, at admission, significantly higher glucose concentrations compared with children with good outcomes (mean SD): 20.0 (7.1) v 9.31 (4.0) mmol/l, p < 0.01), and lower potassium concentrations compared with children with good, moderate, and severe outcomes (mean (SD): 2.8 (0.4) v 3.7 (0.4) mmol/l, p < 0.001, 3.5 (0.3) mmol/l, p < 0.01, and 3.41 (0.3) mmol/l, p < 0.05, respectively). These findings allow for an early allocation of effort and resources to children injured from such falls. (+info)
Temporal responses of oxidative vs. glycolytic skeletal muscles to K+ deprivation: Na+ pumps and cell cations.
When K+ output exceeds input, skeletal muscle releases intracellular fluid K+ to buffer the fall in extracellular fluid (ECF) K+. To investigate the mechanisms and muscle specificity of the K+ shift, rats were fed K+-deficient chow for 2-10 days, and two muscles at phenotypic extremes were studied: slow-twitch oxidative soleus and fast-twitch glycolytic white gastrocnemius (WG). After 2 days of low-K+ chow, plasma K+ concentration ([K+]) fell from 4.6 to 3.7 mM, and Na+-K+-ATPase alpha2 (not alpha1) protein levels in both muscles, measured by immunoblotting, decreased 36%. Cell [K+] decreased from 116 to 106 mM in soleus and insignificantly in WG, indicating that alpha2 can decrease before cell [K+]. After 5 days, there were further decreases in alpha2 (70%) and beta2 (22%) in WG, not in soleus, whereas cell [K+] decreased and cell [Na+] increased by 10 mM in both muscles. By 10 days, plasma [K+] fell to 2.9 mM, with further decreases in WG alpha2 (94%) and beta2 (70%); cell [K+] fell 19 mM in soleus and 24 mM in WG compared with the control, and cell [Na+] increased 9 mM in soleus and 15 mM in WG; total homogenate Na+-K+-ATPase activity decreased 19% in WG and insignificantly in soleus. Levels of alpha2, beta1, and beta2 mRNA were unchanged over 10 days. The ratios of alpha2 to alpha1 protein levels in both control muscles were found to be nearly 1 by using the relative changes in alpha-isoforms vs. beta1- (soleus) or beta2-isoforms (WG). We conclude that the patterns of regulation of Na+ pump isoforms in oxidative and glycolytic muscles during K+ deprivation mediated by posttranscriptional regulation of alpha2beta1 and alpha2beta2 are distinct and that decreases in alpha2-isoform pools can occur early enough in both muscles to account for the shift of K+ to the ECF. (+info)
Severe muscle weakness due to hypokalemia as a manifestation of small-cell carcinoma.
We describe the case of a 56-year-old man with severe muscle weakness due to heavy hypokalemia (serum potassium 1.44 mmol/l) associated with inappropriate kaliuria and alkalemia. Subsequent investigation revealed the presence of ectopic ACTH hypersecretion due to a small-cell lung carcinoma. A significant clinical/laboratory improvement was achieved following chemotherapy-induced regression of the primary tumor. The profound hypokalemia was probably the result of cortisol hypersecretion, which in concert with the ACTH-induced decreased 11beta-hydroxysteroid dehydrogenase activity can exhibit an increased mineralocorticoid activity. In addition, other ACTH-dependent mineralocorticoids may play a contributory role in the development of severe hypokalemia. (+info)
The relationship between distal tubular proton secretion and dietary potassium depletion: evidence for up-regulation of H+ -ATPase.
BACKGROUND: Dietary potassium depletion is associated with elevated plasma bicarbonate concentration and enhanced bicarbonate reabsorption in the distal tubule. The relationship between distal proton secretion and potassium status was investigated by in vivo microperfusion of the superficial distal tubule. METHODS: Experiments were performed on anaesthetized rats that had been maintained on either a low-potassium or control diet for 3-5 weeks prior to experimentation. The distal tubules were perfused at 10 nl/min with either a standard or a barium chloride-containing solution, and the late distal tubular transepithelial potential difference (Vte) and pH of the luminal fluid were recorded using a double-barrelled voltage and ion-sensitive microelectrode. RESULTS: In control rats, the Vte was -40.7+/-2.4 mV and the tubular fluid pH was 6.44+/-0.07; in potassium-depleted animals, the Vte was -15.0+/-1.4 mV and the pH was 6.76+/-0.03. The pH values in both groups of animals were significantly lower than would be predicted from the Vte and systemic pH for passive H+ distribution, indicating active proton secretion. Moreover, in hypokalaemic rats, this difference from predicted pH was significantly greater than in control animals (control = 0.27+/-0.06 vs. low-potassium = 0.46+/-0.03; P<0.01), suggesting enhanced active proton secretion. During perfusion with a solution containing BaCl2, the late distal tubule Vte became lumen positive in potassium-depleted rats, contrasting with an increased lumen negativity in potassium-replete controls. The barium-induced lumen-positive potential difference observed in the hypokalaemic rats was abolished by intravenous administration of acetazolamide. CONCLUSION: These data are consistent with enhanced electrogenic proton secretion (H+ -ATPase) during dietary potassium deprivation. (+info)
Hypokalaemic paralysis revealing Sjogren syndrome in an elderly man.
A 73 year old white man presented with life threatening hypokalaemic paralysis requiring admission to an intensive care unit. Biochemical investigations showed severe hypokalaemia with hyperchloraemic metabolic acidosis, a spot urine pH of 6.5, and a positive urinary anion gap, establishing the diagnosis of distal renal tubular acidosis. Autoimmune tests revealed Sjogren syndrome as the underlying cause of the distal renal tubular acidosis. Full recovery followed potassium and alkali replacement. This dramatic presentation of Sjogren syndrome has not previously been reported in an elderly man. (+info)