Potassium transporters in plants--involvement in K+ acquisition, redistribution and homeostasis

Potassium is a major plant nutrient which has to be accumulated in great quantity by roots and distributed throughout the plant and within plant cells. Membrane transport of potassium can be mediated by potassium channels and secondary potassium transporters. Plant potassium transporters are present in three families of membrane proteins: the K(+) uptake permeases (KT/HAK/KUP), the K(+) transporter (Trk/HKT) family and the cation proton antiporters (CPA). This review will discuss the contribution of members of each family to potassium acquisition, redistribution and homeostasis.

High level of extracellular potassium and its correlates after severe head injury: relationship to high intracranial pressure

OBJECT: Disturbed ionic and neurotransmitter homeostasis are now recognized as probably the most important mechanisms contributing to the development of secondary brain swelling after traumatic brain injury (TBI). Evidence obtained in animal models indicates that posttraumatic neuronal excitation by excitatory amino acids leads to an increase in extracellular potassium, probably due to ion channel activation. The purpose of this study was therefore to measure dialysate potassium in severely head injured patients and to correlate these results with measurements of intracranial pressure (ICP), patient outcome, and levels of dialysate glutamate and lactate, and cerebral blood flow (CBF) to determine the role of ischemia in this posttraumatic ion dysfunction. METHODS: Eighty-five patients with severe TBI (Glasgow Coma Scale Score < 8) were treated according to an intensive ICP management-focused protocol. All patients underwent intracerebral microdialyis. Dialysate potassium levels were analyzed using flame photometry, and dialysate glutamate and dialysate lactate levels were measured using high-performance liquid chromatography and an enzyme-linked amperometric method in 72 and 84 patients, respectively. Cerebral blood flow studies (stable xenon computerized tomography scanning) were performed in 59 patients. In approximately 20% of the patients, dialysate potassium values were increased (dialysate potassium > 1.8 mM) for 3 hours or more. A mean amount of dialysate potassium greater than 2 mM throughout the entire monitoring period was associated with ICP above 30 mm Hg and fatal outcome, as were progressively rising levels of dialysate potassium. The presence of dialysate potassium correlated positively with dialysate glutamate (p < 0.0001) and lactate (p < 0.0001) levels. Dialysate potassium was significantly inversely correlated with reduced CBF (p = 0.019). CONCLUSIONS: Dialysate potassium was increased after TBI in 20% of measurements. High levels of dialysate potassium were associated with increased ICP and poor outcome. The simultaneous increase in dialysate potassium, together with dialysate glutamate and lactate, supports the concept that glutamate induces ionic flux and consequently increases ICP, which the authors speculate may be due to astrocytic swelling. Reduced CBF was also significantly correlated with increased levels of dialysate potassium. This may be due to either cell swelling or altered vasoreactivity in cerebral blood vessels caused by higher levels of potassium after trauma. Additional studies in which potassium-sensitive microelectrodes are used are needed to validate these ionic events more clearly.

High extracellular potassium and its correlates after severe head injury: relationship to high intracranial pressure

Disturbed ionic and neurotransmitter homeostasis are now recognized to be probably the most important mechanisms contributing to the development of secondary brain swelling after traumatic brian injury (TBI). Evidence obtained from animal models indicates that posttraumatic neuronal excitation via excitatory amino acids leads to an increase in extracellular potassium, probably due to ion channel activation. The purpose of this study was therefore to measure dialysate potassium in severely head injured patients and to correlate these results with intracranial pressure (ICP), outcome, and also with the levels of dialysate glutamate, lactate, and cerebral blood flow (CBF) so as to determine the role of ischemia in this posttraumatic ionic dysfunction. Eighty-five patients with severe TBI (Glasgow Coma Scale score < 8) were treated according to an intensive ICP management-focused protocol. All patients underwent intracerebral microdialyis. Dialysate potassium levels were analyzed by flame photometry, as were dialysate glutamate and dialysate lactate levels, which were measured using high-performance liquid chromatography and an enzyme-linked amperometric method in 72 and 84 patients respectively. Cerebral blood flow studies (stable Xenon--computerized tomography scanning) were performed in 59 patients. In approximately 20% of the patients, potassium values were increased (dialysate potassium > 1.8 mmol). Mean dialysate potassium (> 2 mmol) was associated with ICP above 30 mm Hg and fatal outcome. Dialysate potassium correlated positively with dialysate glutamate (p < 0.0001) and lactate levels (p < 0.0001). Dialysate potassium was significantly inversely correlated with reduced CBF (p = 0.019). Dialysate potassium was increased after TBI in 20% of measurements. High levels of dialysate potassium were associated with increased ICP and poor outcome. The simultaneous increase of potassium, together with dialysate glutamate and lactate, supports the hypothesis that glutamate induces ionic flux and consequently increases ICP due to astrocytic swelling. Reduced CBF was also significantly correlated with increased levels of dialysate potassium. This may be due to either cell swelling or altered potassium reactivity in cerebral blood vessels after trauma.

Determinants of cerebral extracellular potassium after severe human head injury

The key role players of brain swelling seen after severe human head injury have only been partly determined. We used our human head injury data base to determine relationships between potassium, glutamate, lactate and cerebral blood flow (CBF). A total of 70 severely head injured patients (GCS < or = 8) were studied using intracerebral microdialysis to measure extracellular glutamate, potassium and lactate. Xenon CT was used to determine regional cerebral blood flow (rCBF). The mean +/- SEM of the r value of all patients, between potassium and glutamate, and potassium and lactate was 0.25 +/- 0.04 (p < 0.0001) and 0.17 +/- 0.06 (p = 0.006), respectively, demonstrating in both cases a positive relationship. rCBF was negatively correlated with potassium with marginal significance (r = -0.35, p = 0.08). When separated into two groups, patients with contusion had higher potassium levels than patients without contusion (1.55 +/- 0.03 mmol/l versus 1.26 +/- 0.02 mmol/l, respectively). These results in severely head injured patients confirm previous in vitro and animal studies in which relationships between potassium, glutamate, lactate and CBF were found. Potassium efflux is a major determinant of cell swelling leading to clinically significant cytotoxic edema due to increased glutamate release during reduced cerebral blood flow.

Expansion of mortar bars in the presence of potassium acetate deicer

Carboxylate-based deicing and anti-icing chemicals became widely used in the mid 1990s, replacing more environmentally burdensome chemicals. Within a few years of their adoption, distress of portland cement concrete runways was reported by a few airports using the new chemicals. Distress manifested characteristics identical to that of alkali silica reactivity (ASR), but onset occurred early in the pavement’s operating life and with pavements thought to contain innocuous aggregate. The carboxylate-based deicing chemicals were suspected of exacerbating ASR-like expansion. Innocuous, moderately, and highly reactive aggregates were tested using modified ASTM C1260 and ASTM C1567 procedures with soak solutions containing deicer solutions and sodium hydroxide or potassium hydroxide. ASR-like expansion is exacerbated in the presence of potassium acetate. The expansion rate produced by a given aggregate is also a function of the alkali hydroxide used. Petrographic analyses were performed on thin sections prepared from mortar bars used in the experiments. Expansion occurred via two mechanisms; rupture of aggregate grains and expansion of paste.

Recent advances in understanding Marfan syndrome: should we now treat surgical patients with losartan?

OBJECTIVE: Marfan syndrome is a systemic connective tissue disorder caused by mutations in the fibrillin-1 gene. It was originally believed that Marfan syndrome results exclusively from the production of abnormal fibrillin-1 that leads to structurally weaker connective tissue when incorporated into the extracellular matrix. This effect seemed to explain many of the clinical features of Marfan syndrome, including aortic root dilatation and acute aortic dissection, which represent the main causes of morbidity and mortality in Marfan syndrome. METHODS: Recent molecular studies, most based on genetically defined mouse models of Marfan syndrome, have challenged this paradigm. These studies established the critical contribution of fibrillin-1 haploinsufficiency and dysregulated transforming growth factor-beta signaling to disease progression. RESULTS: It seems that many manifestations of Marfan syndrome are less related to a primary structural deficiency of the tissues than to altered morphogenetic and homeostatic programs that are induced by altered transforming growth factor-beta signaling. Most important, transforming growth factor-beta antagonism, through transforming growth factor-beta neutralizing antibodies or losartan (an angiotensin II type 1 receptor antagonist), has been shown to prevent and possibly reverse aortic root dilatation, mitral valve prolapse, lung disease, and skeletal muscle dysfunction in a mouse model of Marfan syndrome. CONCLUSION: There are indicators that losartan, a drug widely used to treat arterial hypertension in humans, offers the first potential for primary prevention of clinical manifestations in Marfan syndrome.

Comparison of low potassium Euro-Collins solution and standard Euro-Collins solution in an extracorporeal rat heart-lung model

OBJECTIVE: Euro-Collins solution (EC) is routinely used in lung transplantation. The high potassium of EC, however, may damage the vascular endothelium, thereby contributing to postischemic reperfusion injury. To assess the influence of the potassium concentration on lung preservation, we evaluated the effect of a "low potassium Euro-Collins solution" (LPEC), in which the sodium and potassium concentrations were reversed. METHODS: In an extracorporeal rat heart-lung model lungs were preserved with EC and LPEC. The heart-lung blocks (HLB) were perfused with Krebs-Henseleit solution containing washed bovine red blood cells and ventilated with room air. The lungs were perfused via the working right ventricle with deoxygenated perfusate. Oxygenation and pulmonary vascular resistance (PVR) were monitored. After baseline measurements, hearts were arrested with St. Thomas' solution and the lungs were perfused with EC or LPEC, or were not perfused (controls). The HLBs were stored for 5 min or 2 h ischemic time at 4 degrees C. Reperfusion and ventilation was performed for 40 min. At the end of the trial the wet/dry ratio of the lungs was calculated and light microscopic assessment of the degree of edema was performed. RESULTS: After 5 min of ischemia oxygenation was significantly better in both preserved groups compared to the controls. Pulmonary vascular resistance was elevated in all three groups after 30 min reperfusion at both ischemic times. After 2 h of ischemia PVR of the group preserved with LPEC was significantly lower than those of the EC and controls (LPEC-5 min: 184 +/- 65 dynes * sec * cm-5, EC-5 min: 275 +/- 119 dynes * sec * cm * cm-5, LPEC-2 h: 324 +/- 47 dynes * sec * m-5, EC-2 h: 507 +/- 83 dynes * sec * cm-5). Oxygenation after 2 h of ischemia and 30 min reperfusion was significantly better in the LPEC group compared to EC and controls (LPEC: 70 +/- 17 mmHg, EC: 44 +/- 3 mmHg). The wet/dry ratio was significantly lower in the two preserved groups compared to controls (LPEC-5 min: 5.7 +/- 0.7, EC-5 min: 5.8 +/- 1.2, controls-5 min: 7.5 +/- 1.8, LPEC-2 h: 6.7 +/- 0.4, EC: 6.9 +/- 0.4, controls-2 h: 7.3 +/- 0.4). CONCLUSIONS: We thus conclude that LPEC results in better oxygenation and lower PVR in this lung preservation model. A low potassium concentration in lung preservation solutions may help in reducing the incidence of early graft dysfunction following lung transplantation.

Glycyrrhetinic acid food supplementation lowers serum potassium concentration in chronic hemodialysis patients

Hyperkalemia is a common life-threatening problem in hemodialysis patients. Because glycyrrhetinic acid (GA) inhibits the enzyme 11beta-hydroxy-steroid dehydrogenase II and thereby increases cortisol availability to the colonic mineralocorticoid receptor, it has the potential to lower serum potassium concentrations. To test this, 10 patients in a 6 month prospective, double-blind, placebo-controlled crossover study were given cookies or bread rolls supplemented with glycyrrhetinic acid or placebo. Twenty-four-hour blood pressure measurements were performed at baseline and week 6 and 12 of each treatment period. The ratio of plasma cortisol/cortisone was significantly increased in all patients on GA as compared to baseline or placebo, indicating appropriate enzyme inhibition. Nine of the 10 patients had a persistent decrease in predialysis serum potassium concentration. On GA, mean predialysis serum potassium was significantly lower than at baseline or on placebo. On placebo, serum potassium was significantly elevated above the upper limit of normal in 76% compared to 30% of measurements during GA treatment. Furthermore, on this treatment the frequency of severe hyperkalemia significantly decreased from 9% to 0.6%. No differences were found in parameters reflecting sodium retention. Although these studies show that prolonged GA supplementation persistently lowers serum potassium in dialysis patients, a long-term toxicity study will be mandatory before we recommend the routine use of this treatment.

Potentiometric platform for the quantification of cellular potassium efflux

Renewed interest in the measurement of cellular K(+) effluxes has been prompted by the observation that potassium plays an active and important role in numerous key cellular events, in particular cell necrosis and apoptosis. Although necrosis and apoptosis follow different pathways, both induce intracellular potassium effluxes. Here, we report the use of potassium-selective microelectrodes located in a microfluidic platform for cell culture to monitor and quantify such effluxes in real time. Using this platform, we observed and measured the early signs of cell lysis induced by a modification of the extracellular osmolarity. Furthermore, we were able to quantify the number of dying cells by evaluating the extracellular potassium concentration. A comparison between the potentiometric measurement with a fluorescent live-dead assay performed under similar conditions revealed the delay between potassium effluxes and cell necrosis. These results suggest that such platforms may be exploited for applications, such as cytotoxicological screening assays or tumor cell proliferation assays, by using extracellular K(+) as cell death marker.

MQN-Mapplet: Visualization of Chemical Space with Interactive Maps of DrugBank, ChEMBL, PubChem, GDB-11, and GDB-13

The MQN-mapplet is a Java application giving access to the structure of small molecules in large databases via color-coded maps of their chemical space. These maps are projections from a 42-dimensional property space defined by 42 integer value descriptors called molecular quantum numbers (MQN), which count different categories of atoms, bonds, polar groups, and topological features and categorize molecules by size, rigidity, and polarity. Despite its simplicity, MQN-space is relevant to biological activities. The MQN-mapplet allows localization of any molecule on the color-coded images, visualization of the molecules, and identification of analogs as neighbors on the MQN-map or in the original 42-dimensional MQN-space. No query molecule is necessary to start the exploration, which may be particularly attractive for nonchemists. To our knowledge, this type of interactive exploration tool is unprecedented for very large databases such as PubChem and GDB-13 (almost one billion molecules). The application is freely available for download at www.gdb.unibe.ch.