Potassium Regulation Research Articles

Potassium dynamics in sickle cell anemia: clinical implications and pathophysiological insights

Potassium dynamics are critical in the pathophysiology of sickle cell anemia (SCA), a genetic disorder characterized by the presence of abnormally shaped red blood cells that lead to various complications such as vaso-occlusive crises and hemolytic anemia. This review focuses on the clinical implications and pathophysiological insights of potassium regulation in SCA, highlighting its impact on disease progression and potential therapeutic strategies. The dysregulation of potassium transport in SCA leads to significant K+ efflux and cellular dehydration, exacerbating the sickling process. Dehydrated sickle cells, due to potassium loss, become more rigid and prone to causing blockages in small blood vessels, leading to painful vaso-occlusive crises and ischemia. Furthermore, chronic hemolysis in SCA, aggravated by potassium imbalance, contributes to severe anemia and systemic complications. These insights underscore the importance of maintaining potassium homeostasis to mitigate disease severity and improve patient outcomes. Therapeutic strategies targeting potassium regulation show promise in managing SCA. Inhibitors of the Gardos channel, such as senicapoc, have demonstrated potential in reducing sickling and hemolysis. Additionally, hydration therapy plays a crucial role in maintaining electrolyte balance and preventing RBC dehydration. A comprehensive approach that includes monitoring and correcting electrolyte imbalances, along with standard treatments like hydroxyurea and blood transfusions, is essential for effective disease management.

Role of mTORC2 in Aldosterone-Independent Potassium Regulation: Resolution of the Aldosterone Paradox

Role of mTORC2 in Aldosterone-Independent Potassium Regulation: Resolution of the Aldosterone Paradox

The Na+/K+-ATPase generically enables deterministic bursting in class I neurons by shearing the spike-onset bifurcation structure.

Slow brain rhythms, for example during slow-wave sleep or pathological conditions like seizures and spreading depolarization, can be accompanied by oscillations in extracellular potassium concentration. Such slow brain rhythms typically have a lower frequency than tonic action-potential firing. They are assumed to arise from network-level mechanisms, involving synaptic interactions and delays, or from intrinsically bursting neurons. Neuronal burst generation is commonly attributed to ion channels with slow kinetics. Here, we explore an alternative mechanism generically available to all neurons with class I excitability. It is based on the interplay of fast-spiking voltage dynamics with a one-dimensional slow dynamics of the extracellular potassium concentration, mediated by the activity of the Na+/K+-ATPase. We use bifurcation analysis of the complete system as well as the slow-fast method to reveal that this coupling suffices to generate a hysteresis loop organized around a bistable region that emerges from a saddle-node loop bifurcation-a common feature of class I excitable neurons. Depending on the strength of the Na+/K+-ATPase, bursts are generated from pump-induced shearing the bifurcation structure, spiking is tonic, or cells are silenced via depolarization block. We suggest that transitions between these dynamics can result from disturbances in extracellular potassium regulation, such as glial malfunction or hypoxia affecting the Na+/K+-ATPase activity. The identified minimal mechanistic model outlining the sodium-potassium pump's generic contribution to burst dynamics can, therefore, contribute to a better mechanistic understanding of pathologies such as epilepsy syndromes and, potentially, inform therapeutic strategies.

Product regulation of potassium catalyzed pyrolysis of Chinese Baijiu grains: Towards the production of combustible gases and the reduction of tar formation

Engineering-scale conversion and utilization of Chinese baijiu grains (BG) is imperative for the sustainable development of Chinese Baijiu industry. In this study, we developed a facile catalytic pyrolysis of BG using potassium acetate and investigated the proportions of the solid, liquid, and gaseous products at different temperatures and catalyst loadings. Both parameters affected the product proportions, and the highest combustible gas content (83.3 % of total gaseous products) was observed with 1.0 mol/L potassium acetate at 800 °C. The catalyst also affected the proportion of liquid products. In particular, the bio-oil quality improved and the tar content decreased owing to a decrease in long-chain aliphatic acid and ester contents (<10 % of the total liquid products with 1.0 mol/L potassium acetate at 800 °C) and an increase in hydrocarbon content. In addition, the oxygenated groups in the biochar obtained after pyrolysis were bonded to K via K–O bonds, thus making K@biochar a good controlled-release potassium fertilizer. We believe that our catalytic strategy, which has the abovementioned multiple favorable outcomes, could promote commercial-scale valorization of BG.

Potassium regulation could be key to healthy brain ageing.

Potassium regulation could be key to healthy brain ageing.

Renal potassium regulation in a pig model of therapeutic hypothermia

Therapeutic hypothermia is increasingly utilized clinically to reduce tissue metabolism and protect against neurological damage in cases of cardiac arrest, traumatic brain injury or perinatal hypoxic ischemia. With even mild exposure to hypothermia, hypokalemia develops purportedly due to transcellular potassium shifts resulting in decreased circulating potassium levels. Renal dysfunction with body temperature cooling has also been postulated to potentially contribute to development of sustained hypokalemia. In this study, we used a pig model of controlled acute hypothermia without confounding hypotension and hypoxemia, to test the hypothesis that renal handling of potassium remains intact in hypothermia and is not the cause of decreased circulating plasma potassium seen with body cooling. Anesthetized, mechanically ventilated Duroc cross young pigs (n=25, body weight = 10.0 ± 0.4 kg, male or female) were catheterized for hemodynamic monitoring, regional blood flow assessment via colored microspheres, and urine collection. After baseline values were obtained, pigs were divided into a control normothermia group (n=12) with body temperature maintained at 38.4 ± 0.1 oC or a hypothermia group (n=13) with core body temperature cooled to 34.5 ± 0.1 oC and hypothermia sustained for 2 hours. Hypothermia reduced tissue metabolism as indicated by a decrease in oxygen consumption (VO2= 5.2 ± 0.2 ml/kg in normothermia vs 3.7 ± 0.3 ml/kg in hypothermia. Mean arterial pressure (68± 3 mm Hg) and cardiac output (199 ± 21 ml/min/kg) were not different between groups. Even with the short duration of cold exposure, plasma potassium was lower (p&lt;0.05) within 2 hours of hypothermia (4.1 ± 0.1 mEq/L) vs control (4.8 ± 0.1 mEq/L). Cold exposure caused redistribution of blood flow to the small intestines from other internal organs. Renal blood flow tended to decrease with cold, but glomerular filtration rate was suffcient to maintain urine flow, sodium excretion and free water clearance. Potassium clearance, however, was lower (p&lt;0.05) in hypothermia (0.70 ± 0.07 ml/min/kg) than in normothermia (1.04 ± 0.07 ml/min/kg), with lower potassium excretion (hypothermia = 2997 ± 331 mEq/min vs control = 4784 ± 393 mEq/min, p&lt;0.05) and fractional excretion of potassium. Reduced renal potassium excretion is consistent with renal compensation for lower circulating potassium induced by hypothermia. Interestingly, with relatively higher blood flow to the small intestines compared to decreased blood flow of other internal organs, potassium secretion in the early colon may contribute to further potassium wasting in hypothermia. The rapid initiation of decreased potassium circulating levels with hypothermia supports the thesis of temperature sensitive cell membrane potassium channels affecting extracellular to intracellular shifts of potassium. Results of this study indicate that renal potassium regulation is maintained in hypothermia and functions to decrease urinary potassium loss in the face of hypokalemia. The views expressed are those of the authors and do not necessarily reflect the offcial policy or position of the Defense Health Agency, Department of the Army, Department of Defense, or the U.S. Government. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A modeling analysis of whole body potassium regulation on a high-potassium diet: proximal tubule and tubuloglomerular feedback effects.

Potassium (K+) is an essential electrolyte that plays a key role in many physiological processes, including mineralcorticoid action, systemic blood-pressure regulation, and hormone secretion and action. Indeed, maintaining K+ balance is critical for normal cell function, as too high or too low K+ levels can have serious and potentially deadly health consequences. K+ homeostasis is achieved by an intricate balance between the intracellular and extracellular fluid as well as balance between K+ intake and excretion. This is achieved via the coordinated actions of regulatory mechanisms such as the gastrointestinal feedforward effect, insulin and aldosterone upregulation of Na+-K+-ATPase uptake, and hormone and electrolyte impacts on renal K+ handling. We recently developed a mathematical model of whole body K+ regulation to unravel the individual impacts of these regulatory mechanisms. In this study, we extend our mathematical model to incorporate recent experimental findings that showed decreased fractional proximal tubule reabsorption under a high-K+ diet. We conducted model simulations and sensitivity analyses to investigate how these renal alterations impact whole body K+ regulation. Model predictions quantify the sensitivity of K+ regulation to various levels of proximal tubule K+ reabsorption adaptation and tubuloglomerular feedback. Our results suggest that the reduced proximal tubule K+ reabsorption under a high-K+ diet could achieve K+ balance in isolation, but the resulting tubuloglomerular feedback reduces filtration rate and thus K+ excretion.NEW & NOTEWORTHY Potassium homeostasis is maintained in the body by a complex system of regulatory mechanisms. This system, when healthy, maintains a small extracellular potassium concentration, despite large fluctuations of dietary potassium. The complexities of the system make this problem well suited for investigation with mathematical modeling. In this study, we extend our mathematical model to consider recent experimental results on renal potassium handling on a high potassium diet and investigate the impacts from a whole body perspective.

Systematic review/meta-analysis and a cross-sectional study to assess effects of potassium supplementation on the renin-angiotensin-aldosterone system (RAAS) and blood pressure

Abstract Introduction Nutritional medicine plays a key role in disease prevention and treatment, and we pharmacists must consider our contribution beyond our role in dispensing. Apart from the Dietary Approaches to Stop Hypertension (DASH) diet1, there is a paucity of data on the benefits of nutritional interventions in hypertension with no clear recommendation on potassium in the NICE guidelines. Potassium has been an area of interest in clinical medicine over the decades because of its effect on cardiovascular disease. However, its mechanism of action is poorly understood, and it is unclear it differs between different ethnic groups. Dietary potassium decreases blood pressure (BP) but can also stimulate aldosterone production2. However, the magnitude of potassium-dependent regulation of aldosterone secretion in humans is not fully characterised and it is not clear whether this is mediated by activation of the renin-angiotensin-aldosterone system (RAAS) as a result of a reduction in BP or other mechanisms. Aim To perform a (1) systematic review and meta-analysis of clinical trials assessing effects of potassium on plasma aldosterone and renin in adult individuals alongside a (2) cross-sectional multi-ethnic study to explore the relationship between potassium intake and aldosterone in hypertension. Methods (1) This study was carried out in accordance with PRISMA guidelines3. The full protocol can be found on the PROSPERO database. (2) Self-defined black or white hypertensives were recruited from the hypertension outpatient clinic at St. Thomas’ Hospital and had aldosterone, renin and a 24-hour urinary potassium collected. The systematic review and meta-analysis on already approved clinical trials and did not require ethnical approval. The cross-sectional study was approved by the local Research Ethics Committee in the UK and written informed consent was obtained from all patients. Results 6395 articles were retrieved, and 124 full-text articles were assessed for eligibility. 36 met the prespecified inclusion/exclusion criteria. Potassium supplementation caused a significant decrease in systolic BP (- 3.69 mmHg [-4.91, -2.46], P&amp;lt;0.001) and increase in serum potassium (+0.37 [0.23, 0.52] mmol/L, P&amp;lt;0.001). There was an increase in plasma aldosterone (standardised difference 0.414 [0.291, 0.537], P&amp;lt;0.001) but no effect on plasma renin activity (+0.033 [-0.07, 0.14], P=0.538]. Meta-regression showed a significant positive correlation between change in plasma aldosterone and change in serum potassium (P&amp;lt;0.001). (2) In 469 subjects (72% black), there was a positive association between the measured 24-hour potassium excretion and aldosterone in black (β = 0.200, P = 0.014) but not in white individuals (P = 0.531). Discussion/Conclusion Potassium supplementation increases plasma aldosterone but not renin. The increase in aldosterone correlates with the raise in serum potassium. In subjects with hypertension, potassium intake is related with aldosterone concentration only in black subjects. Overall, the data supports a RAAS-independent potassium regulation of aldosterone which could be particularly relevant in African origin subjects. Limitations: 1. the systematic review results could not be stratified by ethnicity because most of the studies were performed in Caucasian subjects, 2. Use of background therapy in some studies, variable doses of potassium supplementation and duration of supplementation.

The Molecular Mechanism of Potassium Absorption, Transport, and Utilization in Rice

Potassium is essential for plant growth and development and stress adaptation. The maintenance of potassium homeostasis involves a series of potassium channels and transporters, which promote the movement of potassium ions (K+) across cell membranes and exhibit complex expression patterns and regulatory mechanisms. Rice is a major food crop in China. The low utilization rate of potassium fertilizer limits the yield and quality of rice. Elucidating the molecular mechanisms of potassium absorption, transport, and utilization is critical in improving potassium utilization efficiency in rice. Although some K+ transporter genes have been identified from rice, research on the regulatory network is still in its infancy. Therefore, this review summarizes the relevant information on K+ channels and transporters in rice, covering the absorption of K+ in the roots, transport to the shoots, the regulation pathways, the relationship between K+ and the salt tolerance of rice, and the synergistic regulation of potassium, nitrogen, and phosphorus signals. The related research on rice potassium nutrition has been comprehensively reviewed, the existing research foundation and the bottleneck problems to be solved in this field have been clarified, and the follow-up key research directions have been pointed out to provide a theoretical framework for the cultivation of potassium-efficient rice.

Comparison of Diuretic and Electrolyte Excretory Activity between Compounds of Okra Fruit (Abelmoschus esculentus) and Furosemide

Introduction: Hypertension takes place of being one of the most concerning health issues, leading to increasing rate of death due to its complications. Pharmacological therapy diuretic become one to intervene on hypertension’s pathological sequences through sodium and potassium regulation. Similar diuretic effect can be achieved through fruits and vegetables crop including Okra fruit (Abelmoschus esculentus). Objective: to investigate the diuretic variance of different part of Okra fruit’s (Abelmoschus esculentus). Methods: In total of 8 groups of male Rattus norvegicus rats are sorted into control and intervention groups. As control, the C- Group (negative control group) was given Na- CMC 0.5% suspension, and C+ Group (positive control group) was given furosemide. The experimental groups P1, P2, and P3 were given Okra (Abelmoschus esculentus) whole fruit ethanolic extract; P4, P5, and P6 Group are were given Okra (Abelmoschus esculentus) seedless fruit ethanolic extract within range concentration of 75-300 mg/kg body weight. Urine volume is measured every hour for 6 hours and the 24th hour. Sodium and potassium measurements are executed towards 24-hour urine accumulation. Results: Single dose administration of Okra (Abelmoschus esculentus) fruit significantly increase 5th hour urine volume as compared to furosemide (p &lt; 0.001). Whole fruit of Okra (Abelmoschus esculentus) compared to seedless fruit exhibit no significant increment of urine volume and electrolytes (p &gt; 0.05). Conclusion: Ethanolic extract of Okra (Abelmoschus esculentus) fruit produce similar diuretic effect to furosemide. However, seedless Okra (Abelmoschus esculentus) fruit exerts a higher kaliuretic effect compared to whole fruit and furosemide.

Integrative omics analysis of Rosa chinensis reveals insights into its transcriptome and in silico characterization of potassium transport genes

Potassium is a monovalent cation with an osmotic activity in plants. It comprises 10 to 11% of plant dry weight and has crucial importance in the development and stress mechanism of plants. A well-studied system of K+ channels and transporters is involved in the regulation and transport of potassium from soil to different parts of plants. However, the knowledge of this system in ornamental plants especially in roses is limited. In current research, various omics approaches were utilized to characterize the K+ transport system in China rose (Rosa chinensis). Genomewide analysis revealed that a total of 32 genes were candidates for K+ channels (21) and transporters (11). Based on their conserved domain and motif, these genes were further classified into sub-families as K+ channels: 6 Shakers, 5 TPKs, and K+ transporters: 2 HKTs, 5 KEAs, and 14 KUP/HAK/KTs. Phylogenetic and evolutionary studies revealed that segmental duplication may play an important role in the expansion of this gene family. The cis-elements in promoter region showed that these K+ transport-related genes may be involved in response to various abiotic stresses. RNA-seq analysis and its validation through qRT-PCR showed that a channel gene RcAKT1.2 and two transporter genes RcKUP/HAK/KT11 and RcKUP/HAK/KT13 were potentially involved in the regulation of plant stress response. This research explains the valuable vision for functional assays of K+ transport system in China rose.

Soil potassium regulation by initial K level and acidification degree when subjected to liming: A meta-analysis and long-term field experiment

Potassium (K) is the most commonly neglected macronutrient in global change, especially in acidified areas. Lime is a typical management to eliminate soil acidification in agroecosystem soils; however, its impact on soil K dynamics remains inconsistent under different acidic environments. Here, we combine a meta-analysis based on 407 observations from 89 papers and a long-term experiment to investigate the effect and main driving factors of liming on soil K change. The meta-analysis showed that lime application significantly reduced topsoil exchangeable K (EK) content by an average of 4.8% globally. The decrease in topsoil EK content due to liming depended on various soil properties, crop types, fertilizer regimes, and experiment types. Boosted regression tree analysis showed that initial soil exchangeable K (IEK) and pH were the main factors affecting soil EK change under the lime application. The field experiment results further evidence that the decrease of soil EK after the lime application was mainly due to increased K uptake by the crop, and EK transformed to non-exchangeable K (NEK). The application of lime has a greater impact on reducing subsoil EK content at a higher IEK thresholds. Soil EK showed a significant negative relationship with exchangeable calcium (Ca) and a significant positive relationship with exchangeable aluminum (Al). Redundancy analysis revealed that K input (KI), IEK, lime, Ca, Al, pH, and exchangeable magnesium significantly affected the K in soil and crops. The partial least squares path model showed that lime application and IEK levels combined indirectly influence soil K (EK and NEK) by directly affecting soil Ca and Al, K uptake, and K balances. The findings highlight the importance of the lime effect on K management in globally adverse environmental agroecosystems and indicate the key role of initial soil EK levels and acidification degree for regulating crops to excavate the subsoil potassium when subjected to liming.

KLHL3-dependent WNK4 degradation affected by potassium through the neddylation and autophagy pathway

BackgroundStudies reported that kelch-like protein 3 (KLHL3)-Cullin3(CUL3) E3 ligase ubiquitinated with-no-lysine kinase 4 (WNK4). Impaired WNK4 ubiquitination plays a key role in Familial hyperkalemic hypertension (FHHt, also called pseudohypoaldosteronism type II) which results from overaction of thiazide-sensitive sodium chloride cotransport (NCC). In addition, researchers have also found that dietary potassium deficiency activates NCC along the renal distal convoluted tubule (DCT). However, the underlying mechanism remains unclear about the relationship between potassium and WNK4.MethodsIn the present study, we conducted in vitro and in vivo experiments to confirm that KLHL3-dependent WNK4 degradation is affected by potassium through the neddylation and autophagy pathway. In vitro, the WNK4 and KLHL3 plasmids were cotransfected into HEK293 cell lines by lipofectamine 2000, and then incubated with different potassium concentrations (1mmol/L and 10mmol/L) for 24 h, and further treated with MLN4924 or the autophagy inhibitor or both of MLN4924 and the autophagy inhibitor for another 24 h respectively. In vivo, we created mice that were fed with low or high potassium diets and then were injected MLN4924 in the experimental groups. The expression of WNK4, pWNK4, KLHL3, NEDD8, LC3 ,and P62 was detected by western blotting in vitro and vivo experiments.ResultsWe found that the abundance and phosphorylation of WNK4 increase when neddylation is inhibited both in vitro and vivo. Furthermore, the abundance of pWNK4, WNK4, NEDD8, and KLHL3 was increased in the low potassium (LK) group. Inhibiting autophagy can ameliorate the effect of potassium on the abundance and activity of WNK4 to some extent.ConclusionThese findings suggest a complex regulation of potassium in the degradation of WNK4. Low potassium can activate WNK4, which may be related to neddylation and autophagy, but the mechanism needs to be further studied.

Renal Tubular Acidosis: Recognition and Treatment Strategies

Renal tubular acidosis (RTA) is a group of kidney disorders characterized by impaired renal acidification, leading to disturbances in acid-base balance. This review article provides a comprehensive overview of RTA, including its epidemiology, pathophysiology, clinical presentation, and diagnosis. Three main types of RTA are discussed: distal RTA (Type 1), proximal RTA (Type 2), and hyperkalemic RTA (Type 4). Each type’s underlying causes and mechanisms are explored, highlighting the importance of accurate diagnosis for appropriate management. Diagnostic approaches involving clinical evaluation, laboratory tests, and specialized renal function studies are described in detail. The treatment strategies for each type of RTA are outlined, emphasizing the importance of correcting the acid-base imbalance and managing associated electrolyte abnormalities. Lifestyle modifications and pharmacological interventions are discussed, including alkali supplementation and potassium regulation. Finally, the need for further research and prospective studies to enhance our understanding of RTA and improve therapeutic interventions is emphasized. Advancements in diagnosis

Hypokalemia/Hyperkalemia and Hyponatremia/Hypernatremia.

Electrolyte disorders are very common in the pediatric population. Derangements in serum sodium and potassium concentrations are among the most frequently seen given the risk factors and comorbidities unique to children. Pediatricians, in both outpatient and inpatient settings, should be comfortable with the evaluation and initial treatment of disturbances in these electrolyte concentrations. However, to evaluate and treat a child with abnormal serum concentrations of sodium or potassium, it is critical to understand the regulatory physiology that governs osmotic homeostasis and potassium regulation in the body. Comprehension of these basic physiologic processes will allow the provider to uncover the underlying pathology of these electrolyte disturbances and devise an appropriate and safe treatment plan.

Protocolo diagnóstico y terapéutico de los trastornos del potasio

98% of the potassium in the body is inside the cells, fundamentally the musculoskeletal cells, while the remaining 2% is extracellular. The normal concentration of potassium in serum is 3.5–5.5mmol/l. Metabolic potassium disorders are some of the most common electrolytic disorders to be found in clinical practice, and they have a variable spectrum of severity. Hypopotassaemia and hyperpotassaemia cause alterations in the polarization of the cell membrane that leaves to a range of clinical manifestations, the most severe of which affect the cardiovascular system. Potassium regulation depends on intake, intra-extracellular exchange and elimination by the kidneys. After consumption potassium is absorbed in the small intestine and 90%-95% is eliminated in the urine and 5%-10% is excreted in the faeces. Knowledge of potassium regulation will be vital when establishing a suitable treatment for hypopotassaemia/hyperpotassaemia.

Weighted gene co-expression network analysis revealed the key pathways and hub genes of potassium regulating cotton root adaptation to salt stress.

Soil salinization is one of the main abiotic stresses affecting cotton yield and planting area. Potassium application has been proven to be an important strategy to reduce salt damage in agricultural production. However, the mechanism of potassium regulating the salt adaptability of cotton has not been fully elucidated. In the present research, the appropriate potassium application rate for alleviating salt damage of cotton based on different K+/Na+ ratios we screened, and a gene co-expression network based on weighted gene co-expression network analysis (WGCNA) using the transcriptome data sets treated with CK (0 mM NaCl), S (150 mM NaCl), and SK8 (150 mM NaCl + 9.38 mM K2SO4) was constructed. In this study, four key modules that are highly related to potassium regulation of cotton salt tolerance were identified, and the mitogen-activated protein kinase (MAPK) signaling pathway, tricarboxylic acid (TCA) cycle and glutathione metabolism pathway were identified as the key biological processes and metabolic pathways for potassium to improve cotton root salt adaptability. In addition, 21 hub genes and 120 key candidate genes were identified in this study, suggesting that they may play an important role in the enhancement of salt adaptability of cotton by potassium. The key modules, key biological pathways and hub genes discovered in this study will provide a new understanding of the molecular mechanism of potassium enhancing salinity adaptability in cotton, and lay a theoretical foundation for the improvement and innovation of high-quality cotton germplasm.

Circadian regulation of dentate gyrus excitability mediated by G-protein signaling.

The central circadian regulator within the suprachiasmatic nucleus transmits time of day information by a diurnal spiking rhythm driven by molecular clock genes controlling membrane excitability. Most brain regions, including the hippocampus, harbor similar intrinsic circadian transcriptional machinery, but whether these molecular programs generate oscillations of membrane properties is unclear. Here, we show that intrinsic excitability of mouse dentate granule neurons exhibits a 24-h oscillation that controls spiking probability. Diurnal changes in excitability are mediated by antiphase G-protein regulation of potassium and sodium currents that reduce excitability during the Light phase. Disruption of the circadian transcriptional machinery by conditional deletion of Bmal1 enhances excitability selectively during the Light phase by removing G-protein regulation. These results reveal that circadian transcriptional machinery regulates intrinsic excitability by coordinated regulation of ion channels by G-protein signaling, highlighting a potential novel mechanism of cell-autonomous oscillations.

Identification of the HAK gene family reveals their critical response to potassium regulation during adventitious root formation in apple rootstock

Adventitious root formation is a bottleneck during vegetative proliferation. Potassium (K+) is an essential macronutrient for plants. K+ accumulation from the soil and its distribution to the different plant organs is mediated by K+ transporters named K+ transporter (KT), K+ uptake (KUP), or high-affinity K+ (HAK). This study aimed to identify members of the HAK gene family in apples and to characterize the effects of K+ supply on adventitious root formation and on the expression of HAK genes and the genes that putatively control auxin transport, signaling, and cell fate during adventitious root formation. In this study, 34 HAK genes (MdHAKs) were identified in the apple (Malus × domestica ‘Golden Delicious’) genome. A phylogenetic analysis divided MdHAKs into four clusters (I, II, III, and IV), comprising 16, 1, 4, and 13 genes, respectively. The syntenic relationships revealed that 62.5% of the total MdHAK genes arise from genomic duplication events. Chromosome location, domain structure, motif analysis, and physico-chemical characteristics were subsequently investigated. Furthermore, the application of K+ indicated the emergence of adventitious roots at 8 d and produced more adventitious roots at 16 d than the K+-free control (CK) treatment. In addition, various MdHAKs showed root-specific expression in B9 apple rootstock stem cuttings and enhanced expression during the initiation and emergence stages of adventitious root formation in response to K+ treatment. Additionally, K+ treatment enhanced the expression levels of MdPIN1, MdPIN2, and MdAUX1. Further data indicated that a higher expression of MdWOX11, MdLBD16, and MdLBD29 and of cell cycle-related genes contributed to the auxin-stimulated adventitious root formation in response to K+.

Epigenome-wide association analysis of pancreatic exocrine cells from high-fat- and normal diet-fed mice and its potential use for understanding the oncogenesis of human pancreatic cancer

Aberrant DNA methylation is associated with oncogenesis of various human cancers, including pancreatic cancer (PC). PC is the seventh most common cancer, and obesity is a known high-risk factor. However, whether obesity influences DNA methylation in pancreatic exocrine cells and if this influences PC development remain unclear. Here, we performed an epigenome-wide analysis of isolated pancreatic exocrine cells obtained from mice with high-fat-diet-induced obesity (DIO). Using the Illumina Mouse Methylation BeadChip array (280K), we identified 316 differentially methylated regions (DMRs) that were enriched for cellular processes, such as DNA repair, transcription regulation, and cell proliferation, which confirmed obesity-related dysregulation of certain metabolic processes in the pancreatic cells in DIO mice. Comparing the DMRs with those in stage IB PC helped identify 82 overlapping DMRs. Three pathways including the cell hypertrophy pathway involving PLC, PKC, SMAD2/3, and TRKA; the metabolic control pathway involving CREB and AMPK; and the potassium regulation pathway involving K+-channels, were shared between the pancreatic exocrine cells from DIO mice and stage IB PC. Enhanced alteration in the methylation level was observed in PC compared to that in DIO mice. These findings indicated that obesity influences DNA methylation in pancreatic exocrine cells of DIO mice, and persistent dysregulation of DNA methylation in individuals with obesity may result in PC development.