Incongruence between new ideas and current concepts fuels scientific progress. Within acid‐balance physiology, an ‐ apparently new ‐ idea of a ‘strong ion difference’ in plasma (SID) was introduced by Stewart some forty years ago 1‐3. SID is ‘the sum of all strong base cation concentrations minus the sum of all strong acid anion concentrations’2, in clinical practice often ([Na+] + [K+] ‐ [Cl‐]) in

Desmoplakin (Dp) is a crucial component of the desmosome, a supramolecular cell junction complex anchoring intermediate filaments. The mechanisms how Dp modulates cell‐cell adhesion are only partially understood. Here, we studied the impact of Dp on the function of desmosomal adhesion molecules, desmosome turnover and intercellular adhesion.

Chromogranin A is a cumbersome protein. Its biochemical properties, its expression profile in a plethora of cells, its multiple fragments and molecular forms, and their presumed biological activities (1). As the name refers to, the protein belongs to a class of granins, which were first defined as proteins involved in the formation and function of secretory granules (2‐4). The other part of the name

The use of calcineurin inhibitors such as cyclosporine A (CsA) for immunosuppression after solid organ transplantation is commonly limited by renal side effects. CsA‐induced deterioration of glomerular filtration rate and sodium retention may be related to juxtaglomerular dysregulation as a result of suppressed cyclooxygenase 2 (COX‐2) and stimulated renin biosynthesis. We tested whether CsA‐induced

Last year, in many ways, was remarkable, also for Acta Physiologica. Strangely, manuscript submissions did not surge during the most rigid periods of lockdown in March and April. Too stunned by the events, not many scientists swapped their pipette for the fountain pen to bring to paper what had long been on their minds. We actually observed an 8%‐decline in submissions during these two months. However

The worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further promote the development of T2D, and the accumulation of toxic lipid metabolites in serum and peripheral organs may contribute to the diabetic phenotype.

Cancer is a heterogeneous disease which can influence many facets of the human physiology. Treatments and therapies of cancer are as diverse as the illness itself and often come with toxic side effects. In many reviews, researchers regularly summarize the newest results and try to untangle the complexity of cancer and cancer‐related research.1 This review aims to connect recent research on the field

The work “Disruption of transverse‐tubular network reduces energy efficiency in cardiac muscle contraction” by Mellor et al1 that appears in this issue of Acta Physiologica brings together the scientific interests and technical skills of two worlds: that of fine intact cardiac muscle energetics and mechanics (eg Tran et al2 and other studies by Loiselle and his collaborators) and the one of disease‐associated

This study by Zhang et al entitled ‘Keratin 1 attenuates hypoxic pulmonary artery hypertension through suppressing pulmonary artery media smooth muscle expansion’ is presented in a recent edition of Acta Physiologica.1 Leading up to this research were at least three key ideas: (a) that keratin 1 (Krt1) is considered the gatekeeper of the skin's innate immune response for its important regulatory role

Adult hippocampal neurogenesis plays an important role in neuronal plasticity and maintenance in mammals. Low‐threshold voltage‐gated T‐type calcium channels produce calcium spikes that increase fast action potentials in newborn cells in the hippocampal dentate gyrus (DG); however, their role in adult hippocampal neurogenesis remains unclear. Here, we demonstrate impaired adult hippocampal neurogenesis

Impairments in cerebral structure and cognitive performance in chronic heart failure (CHF) are critical components of its comorbidity spectrum. Autonomic afferents that arise from cardiac sensory fibres show enhanced activity with CHF. Desensitization of these fibres by local application of resiniferatoxin (RTX) during myocardial infarction (MI) is known to prevent cardiac hypertrophy, sympathetic

cAMP typically signals downstream of Gs‐coupled receptors and regulates numerous cell functions. In β‐cells, cAMP amplifies Ca2+‐triggered exocytosis of insulin granules. Glucose‐induced insulin secretion is associated with Ca2+‐ and metabolism‐dependent increases of the sub‐plasma‐membrane cAMP concentration ([cAMP]pm) in β‐cells, but potential links to canonical receptor signalling are unclear. The

Epigallocatechin‐3‐gallate (EGCG), the major polyphenol found in green tea, exerts multiple protective effects against cardiovascular diseases, including cardiac hypertrophy. However, the molecular mechanism underlying its anti‐hypertrophic effect has not been clarified. This study revealed that EGCG could inhibit pressure overload‐induced cardiac hypertrophy by regulating the PSMB5/Nmnat2/SIRT6‐dependent

Angiotensin converting enzyme‐2 (ACE‐2) is the cell‐surface receptor enabling viral uptake of corona virus 2019 (SARS‐CoV‐2), thus ACE‐2 is a first step towards COVID‐19 disease. ACE‐2 is a metalloenzyme located primarily on the apical surface, and serves as the entry point also for other coronaviruses, including HCoV‐NL63 and SARS‐CoV. Throughout evolution, ACE‐2 precedes renin, suggesting that ACE‐2’s

The two wandering (latin: vagare) vagal nerves are the longest nerves of the parasympathetic nervous system, reaching from the vagal nuclei in the medulla to the colon, straying in the entire abdominal cavity. The nerves possess more afferent than efferent fibres, depending on species and their location—subdiaphragmatic and cervical parts. The neurons of the afferent fibres are located in the jugular

Aberrant uterine contractions can lead to preterm birth and other labour complications and are a significant cause of maternal morbidity and mortality. To investigate the mechanisms underlying dysfunctional uterine contractions, researchers have used experimentally tractable small animal models. However, biological differences between humans and rodents change how researchers select their animal model

Acetylcholine release is vital in the pacing of theta rhythms in the hippocampus. The subiculum is the output region of the hippocampus with different neuronal subtypes that generate theta oscillations during arousal and rapid eye movement sleep. The combination of intrinsic resonance in the hippocampal neurons and the periodic excitation of hippocampal excitatory and inhibitory neurons by cholinergic

Today, heart failure remains a serious global health challenge. It affects more than 6.2 million people in the United States according to the 2019 data and this number is predicted to reach over 8 million by 2030. The ontology of heart failure involves a pathological process termed adverse remodelling, which is defined by cardiomyocyte hypertrophy and fibrosis. In the current issue of Acta Physiologica

To investigate the role of zinc finger homeobox 3 gene (ZFHX3) in tachypacing‐induced mitochondrial dysfunction and explore its molecular mechanisms and potential as a therapeutic target in atrial fibrillation (AF).

Endothelium‐derived hyperpolarization (EDH)‐mediated response plays an essential role in the control of kidney preglomerular circulation, but the identity of the K+ channels involved in this response is still controversial. We hypothesized that large‐ (KCa1.1), intermediate‐ (KCa3.1) and small (KCa2.3) ‐conductance Ca2+‐activated K+ (KCa) channels are expressed in the endothelium of the preglomerular

Renal tissue hypoxia during cardiopulmonary bypass could contribute to the pathophysiology of acute kidney injury. We tested whether renal tissue hypoxia can be alleviated during cardiopulmonary bypass by the combined increase in target pump flow and mean arterial pressure.

In patients with renal disease, high serum phosphate shows a relationship with cardiovascular risk. We speculate that high phosphate (HP) impairs arterial vasodilation via the endothelium and explore potential underlying mechanisms.

Cystic fibrosis patients have an increased risk of developing metabolic alkalosis presumably as a result of altered renal HCO3− handling. In this study, we directly assess the kidneys’ ability to compensate for a chronic base‐load in the absence of functional CFTR.

This study is aimed at investigation of electrophysiological effects of α1‐adrenoreceptor (α1‐AR) stimulation in the rat superior vena cava (SVC) myocardium, which is one of the sources of proarrhythmic activity.

To assess the relation between muscle fibre hypertrophy and myonuclear accretion in relatively small and large muscle fibre size clusters following prolonged resistance exercise training in older adults.

Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. As mitochondrial dysfunction critically contributes to the pathogenesis of MI, intensive research is focused on the development of therapeutic strategies targeting mitochondrial homeostasis. Mitochondria possess a quality control system which maintains and restores their structure and function by regulating mitochondrial

Metabolic syndrome is a major health‐problem concerning approximately 25% of worldwide population. Metabolic syndrome regroups a cluster of five metabolic abnormalities predisposing to Type 2 Diabetes mellitus. Dysbiotic gut microbiota is accompanied by an increase of both intestinal permeability and pathogen‐associated molecular patterns translocation into blood circulation to induce metabolic endotoxemia

Expansion and remodelling of the cerebral vasculature via the induction of pro‐angiogenic genes is a crucial issue in many pathologies. Urrutia et al1 demonstrate how NG2‐derived cells in the brain sense oxygen to promote neurovascular angiogenesis. Master regulator of cellular adaptation to hypoxia, which includes angiogenesis, is the Hypoxia inducible factor (HIF). Three isoforms exist of the cellular

This issue of Acta Physiologica presents the latest work of Dr Zhang and his team concerning the mechanism of activation of small‐conductance Ca2+‐activated K+ (SK) channels, and more precisely the SK2 subtype.1 Indeed, these still poorly understood channels play important roles in the physiology and the pathology of several types of cells. SK channels are encoded by four different genes, namely KCNN1

Two pharmacological principles, one at least 80 years old and another over 60 years old, have recently come to fruition. The first, phlorizin, was thought to cause diabetes, but then a closer look revealed a renal mechanism that was independent of insulin or insulin deficiency. Research into its action facilitated the discovery of sodium‐dependent glucose transporters. The second compound came close

Ghrelin is a gastric hormone with multiple physiological functions, including the stimulation of food intake and adiposity. It is well established that circulating ghrelin levels are closely associated with feeding patterns, rising strongly before a meal and lowering upon food intake. However, the mechanisms underlying the modulation of ghrelin secretion are not fully understood. The purpose of this

Studies in the past 15 years have highlighted the role of the gut microbiota in modulation of host metabolism. The observation that germ‐free (GF) mice are leaner than conventionally raised (CONV) mice and their apparent resistance to diet‐induced obesity (DIO), sparked the interest in dissecting the possible causative role of the gut microbiota in obesity and metabolic diseases. However, discordant

Off cone bipolar cells of the mammalian retina connect to cone photoreceptor synaptic terminals via non‐invaginating flat contacts at a considerable distance from the only established neurotransmitter release site so far, the synaptic ribbon. Diffusion from the ribbon synaptic active zone is considered the most likely mechanism for the neurotransmitter glutamate to reach postsynaptic receptors on the

Adult neurogenesis occurs in two major niches in the brain: the subgranular zone of the hippocampal formation and the ventricular‐subventricular zone. Neurogenesis in both niches is reduced in ageing and neurological disease involving dementia. Exercise can rescue memory by enhancing hippocampal neurogenesis, but whether exercise affects adult neurogenesis in the ventricular‐subventricular zone remains

To explore the functional profile of circulating monocytes and decidual macrophages at term human pregnancy and their contribution to tissue repair upon stimulation ex vivo with decidual factors and the vasoactive intestinal peptide (VIP).

Blood transfusion may improve renal oxygenation during cardiopulmonary bypass (CPB). In an ovine model of experimental CPB, we tested whether increasing blood haemoglobin concentration [Hb] from ~7 g dL−1 to ~9 g dL−1 improves renal tissue oxygenation.

The intraglomerular mesangial cells are located between the glomerular capillaries. Here we hypothesized that mesangial cells regulate the single nephron glomerular filtration rate (snGFR) and that mesangial cells support the integrity of the glomerular filtration barrier.

To assess how blood‐flow‐restricted (BFR) interval‐training affects the capacity of the leg muscles for pH regulation during dynamic exercise in physically trained men.

Reduced A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif member 13 (ADAMTS13) levels are observed in kidney disease. We test whether recombinant human ADAMTS13 (rhADAMTS13) mitigates renal injury in chronic kidney disease (CKD) and the potential mechanisms.

Diabetes impairs insulin‐induced endothelium‐dependent relaxation by reducing nitric oxide (NO) production. GLP‐1, an incretin hormone, has been shown to prevent the development of endothelial dysfunction. In this study, we hypothesized that GLP‐1 would improve the impaired insulin‐induced relaxation response in diabetic mice. We also examined the underlying mechanisms.

To bioscientists and healthcare professionals "dedicated both to scientific truth and to the Hippocratic tradition" (1) , care for human health and wellbeing through all phases of life is the underlying prior objective of all academic efforts. However, care for human life begins even before conception, when e.g. the reduction of parental risk factors paves the way towards a healthy pregnancy (2). Recent

Sexual differentiation is a complex process, not only dependent on the XY sex‐determination system. The environment, nutrition, metabolic status, sleep and pollutants also play a pivotal role. Correspondingly, the Insulin/Insulin‐like Growth Factor (IGF) pathway has been described as a key player of sexual development and reproduction.1 In this issue, Radovic Pletikosic and colleagues demonstrated

Both arginine (Arg) and its precursor citrulline (Cit) have received much interest in the past two decades because of their potential effects on whole‐body nitric oxide (NO) production and augmentation of NO‐dependent signalling pathways. However, the usefulness of Arg supplementation for NO production is questionable because of its high splanchnic first pass metabolism (FPM), which limits its systemic

Kidney research has been one major focus of publications of recent articles published in Acta physiologica. A number of articles deal with the elucidation of kidney disease models1-12 and the role of oxygen regulation in the kidney.13-16 This contribution focusses on articles that deal with kidney disease models and in the second part on articles that are related to the topic hypoxia and oxygen regulation

Natriuretic peptides, BNP and ANP increase renal blood flow in experimental animals. The signalling pathway in human kidney vasculature is unknown. It was hypothesized that BNP and ANP cause endothelium‐independent relaxation of human intrarenal arteries by vascular natriuretic peptide receptor‐A, but not ‐B and ‐C, which is mimicked by agonists of soluble guanylyl cyclase sGC.

Chromogranin A (CgA), a 439‐residue long protein, is an important cardiovascular regulator and a precursor of various bioactive fragments. Under stressful/pathological conditions, CgA cleavage generates the CgA1‐373 proangiogenic fragment. The present work investigated the possibility that human CgA1‐373 influences the mammalian cardiac performance, evaluating the role of its C‐terminal sequence.

The skeletal muscle excitation‐contraction coupling leading to tension development and increased mechanical stimuli change in concert, leaving it difficult to study their respective effect on molecular signalling and following adaptations. In the current issue of Acta Physiologica, Rindom and co‐workers1 further our understanding of these signalling pathways through a series of elegantly designed experiments

In the current issue of Acta Physiologica, Li and colleagues1 demonstrate that the thromboxane‐prostanoid receptor (TP receptor) is the culprit for vascular smooth muscle cell (VSMC) transformation from a contractile (differentiated) to the synthetic (dedifferentiated) phenotype by prostacyclin when the prostacyclin receptor (IP receptor) is deficient. Through a wide array of convincing experiments

There is an increasing awareness of the impact of age and sex on cardiovascular diseases (CVDs). Differences in physiology are suspected. Beta‐adrenoceptors (beta‐ARs) are an important drug target in CVD and potential differences might have significant impact on the treatment of many patients. To investigate whether age and sex affects beta‐AR function, we analysed a large data set on beta‐AR‐induced

MOG1 is a small protein that can bind to small GTPase RAN and regulate transport of RNA and proteins between the cytoplasm and nucleus. However, the in vivo physiological role of mog1 in the heart needs to be fully defined.

Mitochondria are multifaceted organelles representing the ‘powerhouse of cells’ for their function as bioenergetics and biosynthetic hubs. In addition, they play an essential role in the regulation of innate and adaptive immune responses, including host defences against viruses, as well as in inflammatory responses.1 This peculiar role of mitochondria is principally because of the activation of adaptor

Metabolic sources switch from carbohydrates in utero, to fatty acids after birth and then a mix once adults. O‐GlcNAcylation (O‐GlcNAc) is a post‐translational modification considered as a nutrient sensor. The purpose of this work was to assess changes in protein O‐GlcNAc levels, regulatory enzymes and metabolites during the first periods of life and decipher the impact of O‐GlcNAcylation on cardiac

The importance of diagnostic imaging is undisputable for those practicing medicine or those experiencing medical practice as patients or their families. Who could ever imagine modern clinical medicine without imaging techniques such as X‐ray radiography, computed tomography, ultrasound and magnetic resonance imaging? Even microscopy is widely known as an indispensable tool for diagnostic histopathology

1 INTRODUCTION In the current issue of Acta Physiologica, Guessoum et al.1 address a question that has intrigued investigators for decades within kidney and blood pressure research fields. In conditions where the renin‐angiotensin aldosterone system (RAAS) is chronically challenged, the renin‐producing cells increase significantly in number and their localization expands from a juxtaglomerular position

In the presence of a metabolic acid‐base disorder, the kidney is called upon to compensate appropriately, altering the net acid excretion in urine. Metabolic acidosis is normally associated with urine acidification. This process can be appreciated through two different explanatory models. On the one hand, according to the widely adopted approach, pH regulation is achieved with proton (H+) removal through

A growing body of evidence pointed correlation between insulin‐resistance, testosterone level and infertility, but there is scarce information about mechanisms. The aim of this study was to identify the possible mechanism linking the insulin‐resistance with testosterone‐producing‐Leydig‐cells functionality.

Reichmann et al. (this issue, 2020)1 show that histamine H3 receptor (Hrh3) antagonism or knockout (hrh3‐/‐) in zebrafish (Danio rerio) reduce aggressive behavior. With their projections all over the central nervous system in vertebrates, histaminergic neurons attract increasing attention in the pharmaceutical industry, especially for their inhibitory H3 receptors, coupled to Gi/o‐type proteins, autoreceptors

Nicotinamide adenine dinucleotide (NAD) is an abundant cofactor that plays crucial roles in several cellular processes. NAD can be synthesized de novo starting with tryptophan, or from salvage pathways starting with NAD precursors like nicotinic acid (NA), nicotinamide (NAM) or nicotinamide riboside (NR), referred to as niacin/B3 vitamins, arising from dietary supply or from cellular NAD catabolism

Glycogen particles are found in different subcellular localizations, which are utilized heterogeneously in different fibre types during endurance exercise. Although resistance exercise typically involves only a moderate use of mixed muscle glycogen, the hypothesis of the present study was that high‐volume heavy‐load resistance exercise would mediate a pattern of substantial glycogen depletion in specific

A long‐standing culinary practice is to sprinkle a little salt on fruits such as watermelon, tomatoes or cantaloupe to make them taste sweeter. In the current issue of Acta Physiologica, Yasumatsu et al. 1 describe a likely mechanism for this phenomenon. They report for the first time that the sodium‐glucose cotransporter 1 (SGLT1) is expre