Control Of Ionic Homeostasis Research Articles

Hormonal regulation and functional role of the "renal" tubules in the disease vector, Aedes aegypti.

The Aedes aegypti mosquito is a vector responsible for transmitting various arboviruses including dengue and yellow fever. Their ability to regulate the ionic and water composition of their hemolymph is a major physiological phenomenon, allowing the mosquito to adapt to a range of ecological niches. Hematophagus insects, including the female A. aegypti, face the challenge of excess salt and water intake after a blood meal. Post-prandial diuresis is under rigorous control by neuroendocrine factors, acting on the Malpighian "renal" tubules (MTs), to regulate primary urine production. The MTs are made up of two cell types; mitochondria-rich principal cells, which facilitate active transport of Na+ and K+ cations across the membrane, and thin stellate cells, which allows for transepithelial Cl- secretion. The active driving force responsible for ion transport is the apical V-type H+ ATPase, which creates a proton gradient allowing for Na+ and/or K+ cation exchange through cation/H+ antiporters. Additionally, the basolaterally localized Na+-K+-2Cl- cotransporter (NKCC) is responsible for the transport of these ions from the hemolymph into the principal cells. Numerous studies have examined hormonal regulation of the mosquito MTs and identified several diuretics including serotonin (5HT), a calcitonin-related diuretic hormone 31 (DH31), a corticotropin-related factor like diuretic peptide (DH44), a kinin-related diuretic peptide, as well as anti-diuretic factors including CAPA peptides, all of which are known to regulate fluid and ion transport by the MTs. This review therefore focuses on the control of ionic homeostasis in A. aegypti mosquitoes, emphasizing the importance of the MTs, the channels and transporters involved in maintaining hydromineral balance, and the neuroendocrine regulation of both diuresis and anti-diuresis.

Editorial: Mechanisms of Innate Neuroprotection.

The Editorial on the Research Topic Mechanisms of Innate Neuroprotection Two endogenous mechanisms of neuroprotection have been recently described: ischemic preconditioning and ischemic postconditioning. In fact, the concept of tolerance has been introduced long time ago and, remaining in the modern era of medicine, in 1927, the Austrian physician Julius Wagner-Juaregg was awarded the Nobel Prize in medicine for his research on pyrotherapy to treat psychiatric disorders. At that time, patients affected by dementia paralytica were preconditioned by the inoculation of malaria parasites (1). In the present Research Topic, newly characterized mechanisms involved in preconditioning and postconditioning neuroprotection will be discussed in order to provide tools to plan strategies which induce, mimic, or boost these endogenous protective responses. In particular, this Research Topic discusses the most important mechanisms involved in preconditioning and postconditioning, presenting a series of papers that provide up-to-date, state-of-the-art information on molecular and cellular mechanisms involved in the neuroprotective process elicited by these endogenous neuroprotectant strategies during brain ischemia and other neurological disorders, such as seizure and Alzheimer. In particular, these aspects are faced by tackling multiple angles of this complex phenomenon. In the first part of the book, three chapters are dedicated to the innate immune system and inflammation, giving special attention to the role of microglia (Fumagalli et al.), macrophages (Amantea et al.), and to some important modulators such as NF-kB (Lanzillotta et al.). The core of the Research Topic is dedicated to posttranscriptional modifications occurring during pre- and postconditioning. These aspects are discussed in seven chapters, including reviews (Saugstad; Jimenez-Mateos; Aune et al.), hypothesis and theory paper (Gidday), and original research articles (Reynolds et al.; Meller et al.; Flores-Rodriguez et al.), that highlight the importance of epigenetic modifications and their roles in mediating pre- and postconditioning neuroprotection. The role of non-coding RNA, with particular regards to microRNA, in innate neuroprotection is summarized in two up-to-date papers (Saugstad; Jimenez-Mateos). Experimental manipulation of miRNAs and/or their targets to induce pre- or post-stroke protection is also presented, as well as discussion on miRNA responses to current post-stroke therapies. Finally, in the last two chapters are described cellular mechanisms for neuroprotection, giving a special attention to those proteins involved in ionic homeostasis maintenance. In fact, although the mechanisms through which these two endogenous protective strategies exert their effects are not yet fully understood, recent evidence suggest that the maintenance of ionic homeostasis plays a key role in propagating these neuroprotective phenomena. In this last part of the book, it will be reviewed the role of plasmamembrane transporters and ionic channels involved in the control of ionic homeostasis and taking part to the neuroprotection induced by ischemic preconditioning and postconditioning, with particular regards to the Na+/Ca2+ exchangers (NCX), the plasma membrane Ca2+-ATPase (PMCA), the Na+/H+ exchange (NHE), the Na+/K+/2Cl− cotransport (NKCC), and the acid-sensing cation channels (ASICs) (Cuomo et al.). An interesting view from inside organelles is provided in the review by Sisalli et al. We hope that this Research Topic will stimulate the continuing efforts to understand the cell and physiological mechanisms underlying the origin of endogenous neuroprotective mechanisms. The understanding of the mechanisms involved in the neuroprotection elicited by preconditioning and postconditioning will be clinically relevant for it will contribute to discover new druggable targets in neurodegenerative disorder intervention. Therefore, the data presented here will highlight the capacity of ischemic preconditioning and postconditioning to be of benefit to patients.

Ionic homeostasis in brain conditioning.

Most of the current focus on developing neuroprotective therapies is aimed at preventing neuronal death. However, these approaches have not been successful despite many years of clinical trials mainly because the numerous side effects observed in humans and absent in animals used at preclinical level. Recently, the research in this field aims to overcome this problem by developing strategies which induce, mimic, or boost endogenous protective responses and thus do not interfere with physiological neurotransmission. Preconditioning is a protective strategy in which a subliminal stimulus is applied before a subsequent harmful stimulus, thus inducing a state of tolerance in which the injury inflicted by the challenge is mitigated. Tolerance may be observed in ischemia, seizure, and infection. Since it requires protein synthesis, it confers delayed and temporary neuroprotection, taking hours to develop, with a pick at 1–3 days. A new promising approach for neuroprotection derives from post-conditioning, in which neuroprotection is achieved by a modified reperfusion subsequent to a prolonged ischemic episode. Many pathways have been proposed as plausible mechanisms to explain the neuroprotection offered by preconditioning and post-conditioning. Although the mechanisms through which these two endogenous protective strategies exert their effects are not yet fully understood, recent evidence highlights that the maintenance of ionic homeostasis plays a key role in propagating these neuroprotective phenomena. The present article will review the role of protein transporters and ionic channels involved in the control of ionic homeostasis in the neuroprotective effect of ischemic preconditioning and post-conditioning in adult brain, with particular regards to the Na+/Ca2+ exchangers (NCX), the plasma membrane Ca2+-ATPase (PMCA), the Na+/H+ exchange (NHE), the Na+/K+/2Cl− cotransport (NKCC) and the acid-sensing cation channels (ASIC). Ischemic stroke is the third leading cause of death and disability. Up until now, all clinical trials testing potential stroke neuroprotectants failed. For this reason attention of researchers has been focusing on the identification of brain endogenous neuroprotective mechanisms activated after cerebral ischemia. In this context, ischemic preconditioning and ischemic post-conditioning represent two neuroprotecive strategies to investigate in order to identify new molecular target to reduce the ischemic damage.

Fra global til lokal - ny forståelse av den elektromekaniske koblingen i hjertet

The coupling between depolarisation and the heart's contraction is fundamental to the physiology and pathophysiology of the heart. This paper describes how the coupling depends on the interaction between proteins in "microdomains" in the heart muscle cells. The paper is based on the authors'' own research and on a discretionary selection of articles found by means of a literature search in PubMed. Essential aspects of the physiology and pathophysiology of the heart must be understood through the interaction between proteins in delimited parts of the cells. The significance of the binding protein ankyrin-B and the Ca2+ channel IP3R (inositol 1,4,5-triphosphate receptor) is best understood in this context. Abnormal function of ankyrin-B and IP3R is involved in congenital diseases with increased risk of arrhythmia and in weakened contractility and arrhythmia in connection with heart failure. The pathophysiological mechanism involves a change in Ca2+ homeostasis locally in the heart muscle cells. Normal cardiac electromechanical coupling depends on control of ionic homeostasis in intracellular microdomains. Insight into the interaction between proteins in these "local neighbourhoods" provides new explanations for the pathophysiology of heart disease and paves the way for further research on arrhythmia mechanisms in hereditary diseases such as ankyrin-B syndrome.

Neuroendocrine control of ionic homeostasis in blood-sucking insects

The pioneering work of Simon Maddrell established that the rapid postprandial diuresis of the haematophagous insect Rhodnius prolixus is controlled by a diuretic hormone and demonstrated the role of the Malpighian tubules in meeting the volumic, osmotic and ionic challenges posed by an enormous blood meal. A number of diuretic and antidiuretic hormones that control secretion of primary urine by Malpighian tubules have now been identified, but little is known of the interplay between these hormones and those that regulate transport processes in the hindgut. This review therefore focuses on the control of ionic homeostasis in Rhodnius and mosquitoes, because primary urine is voided virtually unchanged during the rapid diuresis that follows a blood meal. At such times, the hindgut has a negligible impact on the volume and composition of the final urine, and neurohormones acting on the Malpighian tubules have a dominant role in the control of ionic homeostasis.