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Molecular Neurobiology Oct 2014Rapid sensation of mechanical stimuli is often mediated by mechanosensitve ion channels. Their opening results from conformational changes induced by mechanical forces.... (Review)
Review
Rapid sensation of mechanical stimuli is often mediated by mechanosensitve ion channels. Their opening results from conformational changes induced by mechanical forces. It leads to membrane permeation of selected ions and thereby to electrical signaling. Newly identified mechanosensitive ion channels are emerging at an astonishing rate, including some that are traditionally assigned for completely different functions. In this review, we first provide a brief overview of ion channels that are known to play a role in mechanosensation. Next, we focus on three representative ones, including the transient receptor potential channel V4 (TRPV4), Kv1.1 voltage-gated potassium (Kv) channel, and Piezo channels. Their structures, biophysical properties, expression and targeting patterns, and physiological functions are highlighted. The potential role of their mechanosensation in related diseases is further discussed. In sum, mechanosensation appears to be achieved in a variety of ways by different proteins and plays a fundamental role in the function of various organs under normal and abnormal conditions.
Topics: Animals; Cell Membrane Permeability; Humans; Ion Channel Gating; Mechanoreceptors; Membrane Proteins; Potassium; Potassium Channels
PubMed: 24532247
DOI: 10.1007/s12035-014-8654-4 -
Biometals : An International Journal on... Oct 2021Magnesium (Mg) is the 2nd most abundant intracellular cation, which participates in various enzymatic reactions; there by regulating vital biological functions.... (Review)
Review
Magnesium (Mg) is the 2nd most abundant intracellular cation, which participates in various enzymatic reactions; there by regulating vital biological functions. Magnesium (Mg) can regulate several cations, including sodium, potassium, and calcium; it consequently maintains physiological functions like impulse conduction, blood pressure, heart rhythm, and muscle contraction. But, it doesn't get much attention in account with its functions, making it a "Forgotten cation". Like other cations, maintenance of the normal physiological level of Mg is important. Its deficiency is associated with various diseases, which point out to the importance of Mg as a drug. The roles of Mg such as natural calcium antagonist, glutamate NMDA receptor blocker, vasodilator, antioxidant and anti-inflammatory agent are responsible for its therapeutic benefits. Various salts of Mg are currently in clinical use, but their application is limited. This review collates all the possible mechanisms behind the behavior of magnesium as a drug at different disease conditions with clinical shreds of evidence.
Topics: Calcium; Cations; Magnesium; Potassium; Sodium
PubMed: 34213669
DOI: 10.1007/s10534-021-00328-7 -
Progress in Neurobiology Oct 2020Throughout the nervous system, ion gradients drive fundamental processes. Yet, the roles of interstitial ions in brain functioning is largely forgotten. Emerging... (Review)
Review
Throughout the nervous system, ion gradients drive fundamental processes. Yet, the roles of interstitial ions in brain functioning is largely forgotten. Emerging literature is now revitalizing this area of neuroscience by showing that interstitial cations (K, Ca and Mg) are not static quantities but change dynamically across states such as sleep and locomotion. In turn, these state-dependent changes are capable of sculpting neuronal activity; for example, changing the local interstitial ion composition in the cortex is sufficient for modulating the prevalence of slow-frequency neuronal oscillations, or potentiating the gain of visually evoked responses. Disturbances in interstitial ionic homeostasis may also play a central role in the pathogenesis of central nervous system diseases. For example, impairments in K buffering occur in a number of neurodegenerative diseases, and abnormalities in neuronal activity in disease models disappear when interstitial K is normalized. Here we provide an overview of the roles of interstitial ions in physiology and pathology. We propose the brain uses interstitial ion signaling as a global mechanism to coordinate its complex activity patterns, and ion homeostasis failure contributes to central nervous system diseases affecting cognitive functions and behavior.
Topics: Animals; Calcium; Cations; Central Nervous System; Humans; Magnesium; Nervous System Physiological Phenomena; Potassium; Signal Transduction
PubMed: 32413398
DOI: 10.1016/j.pneurobio.2020.101802 -
Mayo Clinic Proceedings Aug 2017High sodium intake, whether via diet or drugs, augments cardiorenal risk. Regardless of its source, high sodium intake can both lead to hypertension and reduce the... (Review)
Review
High sodium intake, whether via diet or drugs, augments cardiorenal risk. Regardless of its source, high sodium intake can both lead to hypertension and reduce the efficacy of renin-angiotensin-aldosterone system inhibitors, which are currently guideline-recommended treatments for hypertension, chronic kidney disease, and heart failure. Reducing sodium intake is therefore recommended to reduce the risk of adverse cardiorenal outcomes. An inverse relationship exists between sodium and potassium, with foods high in sodium being lower in potassium. Diets high in potassium have been associated with reducing hypertension and heart failure; however, optimal renin-angiotensin-aldosterone system inhibitor dosing is often limited by hyperkalemia, which can lead to life-threatening cardiac arrhythmias and increased mortality. Potassium binders are effective at reducing potassium levels. Although some use sodium as the potassium exchange ion, thus increasing sodium intake, a new potassium binder uses another exchange ion and therefore does not increase sodium intake. When treatment options require agents that may precipitate hyperkalemia, particularly in patients at high cardiorenal risk, drugs that do not add to the sodium load may be preferred. A literature search was conducted using PubMed; search terms included potassium, sodium, hyperkalemia, potassium binders, and the literature search focused on manuscripts published more recently since 2000.
Topics: Cardiovascular Diseases; Heart Failure; Humans; Hyperkalemia; Potassium; Renal Insufficiency, Chronic; Renin-Angiotensin System; Sodium, Dietary
PubMed: 28778258
DOI: 10.1016/j.mayocp.2017.04.006 -
Current Opinion in Nephrology and... Sep 2017The current review combines past findings with recent advances in our understanding of the homeostatic response to potassium imbalance. (Review)
Review
PURPOSE OF REVIEW
The current review combines past findings with recent advances in our understanding of the homeostatic response to potassium imbalance.
RECENT FINDINGS
Following the ingestion of a dietary potassium load, a combination of extrarenal and renal mechanisms act to maintain extracellular K+ within a tight window. Through hormonal regulation and direct K+ sensing, the nephron is ideally suited to respond to wide shifts in external K+ balance. Current evidence indicates that dietary K+ loading triggers a coordinated kaliuretic response that appears to involve voltage-dependent changes in sodium transport across multiple nephron segments, including the proximal tubule, medullary loop of Henle, and distal tubule. Inhibition of sodium transport in these segments would accomplish the final goal of enhancing distal NaCl delivery, luminal flow, and K+ secretion in the aldosterone sensitive distal nephron (ASDN).
SUMMARY
Ongoing research seeks to define the relationship between potassium and volume homeostasis by elucidating pathways that couple renal K+ sensing and tubular function during the potassium stress response.
Topics: Animals; Homeostasis; Humans; Ion Transport; Nephrons; Potassium; Potassium, Dietary; Sodium; Stress, Physiological
PubMed: 28614118
DOI: 10.1097/MNH.0000000000000352 -
Cells Aug 2022Traumatic spinal cord injury is a life-changing condition with a significant socio-economic impact on patients, their relatives, their caregivers, and even the... (Review)
Review
Traumatic spinal cord injury is a life-changing condition with a significant socio-economic impact on patients, their relatives, their caregivers, and even the community. Despite considerable medical advances, there is still a lack of options for the effective treatment of these patients. The major complexity and significant disabling potential of the pathophysiology that spinal cord trauma triggers are the main factors that have led to incremental scientific research on this topic, including trying to describe the molecular and cellular mechanisms that regulate spinal cord repair and regeneration. Scientists have identified various practical approaches to promote cell growth and survival, remyelination, and neuroplasticity in this part of the central nervous system. This review focuses on specific detailed aspects of the involvement of cations in the cell biology of such pathology and on the possibility of repairing damaged spinal cord tissue. In this context, the cellular biology of sodium, potassium, lithium, calcium, and magnesium is essential for understanding the related pathophysiology and also the possibilities to counteract the harmful effects of traumatic events. Lithium, sodium, potassium-monovalent cations-and calcium and magnesium-bivalent cations-can influence many protein-protein interactions, gene transcription, ion channel functions, cellular energy processes-phosphorylation, oxidation-inflammation, etc. For data systematization and synthesis, we used the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) methodology, trying to make, as far as possible, some order in seeing the "big forest" instead of "trees". Although we would have expected a large number of articles to address the topic, we were still surprised to find only 51 unique articles after removing duplicates from the 207 articles initially identified. Our article integrates data on many biochemical processes influenced by cations at the molecular level to understand the real possibilities of therapeutic intervention-which must maintain a very narrow balance in cell ion concentrations. Multimolecular, multi-cellular: neuronal cells, glial cells, non-neuronal cells, but also multi-ionic interactions play an important role in the balance between neuro-degenerative pathophysiological processes and the development of effective neuroprotective strategies. This article emphasizes the need for studying cation dynamics as an important future direction.
Topics: Calcium; Cations; Humans; Lithium; Magnesium; Potassium; Sodium; Spinal Cord Injuries
PubMed: 36010579
DOI: 10.3390/cells11162503 -
American Journal of Physiology. Renal... Mar 2022The seminal studies conducted by Giebisch and coworkers in the 1960s paved the way for understanding the renal mechanisms involved in K homeostasis. It was demonstrated... (Review)
Review
The seminal studies conducted by Giebisch and coworkers in the 1960s paved the way for understanding the renal mechanisms involved in K homeostasis. It was demonstrated that differential handling of K in the distal segments of the nephron is crucial for proper K balance. Although aldosterone had been classically ascribed as the major ion transport regulator in the distal nephron, thereby contributing to K homeostasis, it became clear that aldosterone per se could not explain the ability of the kidney to modulate kaliuresis in both acute and chronic settings. The existence of alternative kaliuretic and antikaliuretic mechanisms was suggested by physiological studies in the 1980s but only gained form and shape with the advent of molecular biology. It is now established that the kidneys recruit several endocrine and paracrine mechanisms for adequate kaliuretic response. These mechanisms include the direct effects of peritubular K, a gut-kidney regulatory axis sensing dietary K levels, the kidney secretion of kallikrein during postprandial periods, the upregulation of angiotensin II receptors in the distal nephron during chronic changes in K diet, and the local increase of prostaglandins by low-K diet. This review discusses recent advances in the understanding of endocrine and paracrine mechanisms underlying the modulation of K secretion and how these mechanisms impact kaliuresis and K balance. We also highlight important unknowns about the regulation of renal K excretion under physiological circumstances.
Topics: Aldosterone; Homeostasis; Kidney; Nephrons; Potassium
PubMed: 35073212
DOI: 10.1152/ajprenal.00251.2021 -
Nephron 2023Low potassium increases the phosphorylation and activity of the sodium chloride cotransporter (NCC) in the distal convoluted tubule of the nephron, which contributes to... (Review)
Review
BACKGROUND
Low potassium increases the phosphorylation and activity of the sodium chloride cotransporter (NCC) in the distal convoluted tubule of the nephron, which contributes to the hypertensive effect of the modern low potassium/high sodium diet. A central mediator of potassium regulation of NCC is the chloride-sensitive With No Lysine [K] (WNK) kinase.
SUMMARY
Chloride directly inhibits WNKs by binding to the active site. The mechanisms underlying WNK regulation by extracellular potassium are reviewed, as well as the modulatory effect of kidney-specific-WNK1. WNK1, but not WNK1 kinase activity, is also required for the aldosterone-independent regulation of the epithelial sodium channel by potassium. Whether intracellular chloride could be involved in this process is discussed. Recent studies demonstrating direct regulation of WNKs by intracellular potassium are also reviewed, and the potential physiological relevance to renal epithelial ion transport is discussed.
KEY MESSAGES
WNKs are sensors of the intracellular ionic milieu. In the nephron, changes in extracellular ion concentrations, resulting in changes in intracellular ion concentration, regulate WNK activity and downstream transporters and channels to maintain total body ion homeostasis.
Topics: Humans; Protein Serine-Threonine Kinases; Potassium; Chlorides; Nephrons; Kidney Tubules, Distal
PubMed: 35977527
DOI: 10.1159/000526051 -
Progress in Biophysics and Molecular... 2022This retrospective traces the hypothesis of ion channels from an early statement in a 1970 essay in this journal (Hille, B., 1970, Prog. Biophys. Mol. Biol. 21, 1-32) to... (Review)
Review
This retrospective traces the hypothesis of ion channels from an early statement in a 1970 essay in this journal (Hille, B., 1970, Prog. Biophys. Mol. Biol. 21, 1-32) to its realization today in biophysical, molecular, biochemical, and structural terms. The Na and K channels of the action potential have been isolated, reconstituted, cloned, mutated, and expressed. They are conformationally flexible, multi-pass glycosylated membrane proteins. Refined atomic structures of several conformational states are known. The discoveries over this half century history illustrate the growth of a field from initial ideas to a mature discipline of biology, physiology, and biomedical science.
Topics: Ion Channels; Ions; Potassium; Retrospective Studies; Sodium
PubMed: 34856230
DOI: 10.1016/j.pbiomolbio.2021.11.003 -
International Journal of Molecular... Apr 2018Ion channels activated by reactive oxygen species (ROS) have been found in the plasma membrane of charophyte , dicotyledon , and , and the monocotyledon . Their... (Review)
Review
Ion channels activated by reactive oxygen species (ROS) have been found in the plasma membrane of charophyte , dicotyledon , and , and the monocotyledon . Their activities have been reported in charophyte giant internodes, root trichoblasts and atrichoblasts, pollen tubes, and guard cells. Hydrogen peroxide and hydroxyl radicals are major activating species for these channels. Plant ROS-activated ion channels include inwardly-rectifying, outwardly-rectifying, and voltage-independent groups. The inwardly-rectifying ROS-activated ion channels mediate Ca-influx for growth and development in roots and pollen tubes. The outwardly-rectifying group facilitates K⁺ efflux for the regulation of osmotic pressure in guard cells, induction of programmed cell death, and autophagy in roots. The voltage-independent group mediates both Ca influx and K⁺ efflux. Most studies suggest that ROS-activated channels are non-selective cation channels. Single-channel studies revealed activation of 14.5-pS Ca influx and 16-pS K⁺ efflux unitary conductances in response to ROS. The molecular nature of ROS-activated Ca influx channels remains poorly understood, although annexins and cyclic nucleotide-gated channels have been proposed for this role. The ROS-activated K⁺ channels have recently been identified as products of Stellar K⁺ Outward Rectifier () and Guard cell Outwardly Rectifying K⁺ channel () genes.
Topics: Animals; Calcium Signaling; Humans; Hydroxyl Radical; Plants; Potassium; Reactive Oxygen Species
PubMed: 29690632
DOI: 10.3390/ijms19041263