Large Conductance Potassium Channels in the Nervous System

2018 ◽  
Author(s):  
Willy Carrasquel-Ursulaez ◽  
Yenisleidy Lorenzo ◽  
Felipe Echeverria ◽  
Ramon Latorre
Keyword(s):  
Nervous System ◽  
Neurotransmitter Release ◽  
Action Potentials ◽  
Metabolic Regulation ◽  
Α Subunit ◽  
Pathological Conditions ◽  
System P ◽  
Channel Diversity ◽  
Accessory Subunits

The Slowpoke (Slo) family of large conductance K+ channels comprises four structurally and functionally related members (Slo1, Slo2.1, Slo2.2, and Slo3). With the exception of Slo3, all Slo channels are expressed in neurons, where their diverse functions include influencing the shape, frequency, and propagation of action potentials, as well as neurotransmitter release. The Slo1 channel (K Ca 1.1; KCNMA1, BK) is Ca2+- and voltage-activated, while the two Slo2 channels, Slo2.1 (K N a 1.2, KCNT2, Slick) and Slo2.2 (K N a 1.1, KCNT1, Slack), are activated by internal Na+. The functional diversity of the Slo family is greatly increased through alternative splicing, metabolic regulation, and the formation of heterotetramers (Slo2 channels). Co-expression of the pore-forming α subunit of Slo1 with its accessory subunits β and γ further increases channel diversity. This chapter focuses on the role of the Slo channel family in neurons under both physiological and pathological conditions.

Drosophila CAKI/CMG Protein, a Homolog of Human CASK, Is Essential for Regulation of Neurotransmitter Vesicle Release

2005 ◽  
Vol 94 (2) ◽  
pp. 1074-1083 ◽  
Author(s):  
Mauro A. Zordan ◽  
Michele Massironi ◽  
Maria Giovanna Ducato ◽  
Geertruy te Kronnie ◽  
Rodolfo Costa ◽  
...  
Keyword(s):  
Nervous System ◽  
Neurotransmitter Release ◽  
Transmembrane Protein ◽  
Protein A ◽  
Model Organism ◽  
Brain Regions ◽  
Synaptic Activity ◽  
Giant Fiber ◽  
Nervous System Function

Vertebrate CASK is a member of the membrane-associated guanylate kinase (MAGUK) family of proteins. CASK is present in the nervous system where it binds to neurexin, a transmembrane protein localized in the presynaptic membrane. The Drosophila homologue of CASK is CAKI or CAMGUK. CAKI is expressed in the nervous system of larvae and adult flies. In adult flies, the expression of caki is particularly evident in the visual brain regions. To elucidate the functional role of CASK, we employed a caki null mutant in the model organism Drosophila melanogaster. By means of electrophysiological methods, we analyzed, in adult flies, the spontaneous and evoked neurotransmitter release at the neuromuscular junction (NMJ) as well as the functional status of the giant fiber pathway and of the visual system. We found that in caki mutants, when synaptic activity is modified, the spontaneous neurotransmitter release of the indirect flight muscle NMJ was increased, the response of the giant fiber pathway to continuous stimulation was impaired, and electroretinographic responses to single and continuous repetitive stimuli were altered and optomotor behavior was abnormal. These results support the involvement of CAKI in neurotransmitter release and nervous system function.

scholarly journals Role of the Cholinergic Anti-Inflammatory Reflex in Central Nervous System Diseases

2021 ◽  
Vol 22 (24) ◽  
pp. 13427
Author(s):  
Ivan Emmanuel Ramos-Martínez ◽  
María Carmen Rodríguez ◽  
Marco Cerbón ◽  
Juan Carlos Ramos-Martínez ◽  
Edgar Gustavo Ramos-Martínez
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Strategies ◽  
Chemical Stimulation ◽  
Nervous System Diseases ◽  
Central Nervous System Diseases ◽  
Pathological Conditions ◽  
Bidirectional Communication ◽  
Anti Inflammatory

In several central nervous system diseases, it has been reported that inflammation may be related to the etiologic process, therefore, therapeutic strategies are being implemented to control inflammation. As the nervous system and the immune system maintain close bidirectional communication in physiological and pathological conditions, the modulation of inflammation through the cholinergic anti-inflammatory reflex has been proposed. In this review, we summarized the evidence supporting chemical stimulation with cholinergic agonists and vagus nerve stimulation as therapeutic strategies in the treatment of various central nervous system pathologies, and their effect on inflammation.

PECULIARITIES OF FORMING NERVO-MENTAL DISORDERS AND VISUAL IMPAIRMENT AMONG MOSCOW STUDENTS DURING THE LEARNING PROCESS AT SCHOOL

2019 ◽  
pp. 20-27 ◽  
Author(s):  
I.K. Rapoport ◽  
A.P. A.P. Tsameryan
Keyword(s):  
Nervous System ◽  
Visual Impairment ◽  
Chronic Diseases ◽  
Functional Disorders ◽  
School Students ◽  
Whole School ◽  
Pathological Conditions ◽  
Negative Role ◽  
High Level

The peculiarities of the forming the most common functional deviations and chronic diseases in students in the school ontogenesis dynamics are revealed. The morbidity dynamics of functional disorders and chronic diseases of the nervous system and mental sphere is presented. We analyzed changes in the prevalence of functional visual impairment and chronic diseases of the visual analyzer. The course of the pathological processes after the diagnosis of each student was evaluated according to the data of specially developed catamnesis questionnaires. We found a high level of functional disorders’ occurrence frequency of the nervous system and mental sphere (together) in primary school students and the rapid growth rate of the indicator from the 8th to the 11th forms. Visual impairment is characterized by an increase in the prevalence and unfavorable course of pathological processes during the whole school ontogenesis. The revealed functions of deviation and chronic diseases testify to the negative role of excessive academic load of students, psycho-emotional and visual overstrain in the formation of pathological conditions in school students.

Different VAMP/Synaptobrevin Complexes for Spontaneous and Evoked Transmitter Release at the Crayfish Neuromuscular Junction

1998 ◽  
Vol 80 (6) ◽  
pp. 3233-3246 ◽  
Author(s):  
Shao-Ying Hua ◽  
Dorota A. Raciborska ◽  
William S. Trimble ◽  
Milton P. Charlton
Keyword(s):  
Neuromuscular Junction ◽  
Transmitter Release ◽  
Neurotransmitter Release ◽  
Action Potentials ◽  
Neuromuscular Junctions ◽  
Spontaneous Release ◽  
Intracellular Ca ◽  
Crayfish Neuromuscular Junction ◽  
Evoked Transmitter Release

Hua, Shao-Ying, Dorota A. Raciborska, William S. Trimble, and Milton P. Charlton. Different VAMP/synaptobrevin complexes for spontaneous and evoked transmitter release at the crayfish neuromuscular junction. J. Neurophysiol. 80: 3233–3246, 1998. Although vesicle-associated membrane protein (VAMP/synaptobrevin) is essential for evoked neurotransmitter release, its role in spontaneous transmitter release remains uncertain. For instance, many studies show that tetanus toxin (TeNT), which cleaves VAMP, blocks evoked transmitter release but leaves some spontaneous transmitter release. We used recombinant tetanus and botulinum neurotoxin catalytic light chains (TeNT-LC, BoNT/B-LC, and BoNT/D-LC) to examine the role of VAMP in spontaneous transmitter release at neuromuscular junctions (nmj) of crayfish. Injection of TeNT-LC into presynaptic axons removed most of the VAMP immunoreactivity and blocked evoked transmitter release without affecting nerve action potentials or Ca2+ influx. The frequency of spontaneous transmitter release was little affected by the TeNT-LC when the evoked transmitter release had been blocked by >95%. The spontaneous transmitter release left after TeNT-LC treatment was insensitive to increases in intracellular Ca2+. BoNT/B-LC, which cleaves VAMP at the same site as TeNT-LC but uses a different binding site, also blocked evoked release but had minimal effect on spontaneous release. However, BoNT/D-LC, which cleaves VAMP at a different site from the other two toxins but binds to the same position on VAMP as TeNT, blocked both evoked and spontaneous transmitter release at similar rates. The data indicate that different VAMP complexes are employed for evoked and spontaneous transmitter release; the VAMP used in spontaneous release is not readily cleaved by TeNT or BoNT/B. Because the exocytosis that occurs after the action of TeNT cannot be increased by increased intracellular Ca2+, the final steps in neurotransmitter release are Ca2+ independent.

scholarly journals Functional Role of Non-Muscle Myosin II in Microglia: An Updated Review

2021 ◽  
Vol 22 (13) ◽  
pp. 6687
Author(s):  
Chiara Porro ◽  
Antonio Pennella ◽  
Maria Antonietta Panaro ◽  
Teresa Trotta
Keyword(s):  
Nervous System ◽  
Atp Hydrolysis ◽  
Myosin Ii ◽  
Cellular Functions ◽  
Pathological Conditions ◽  
Different Types ◽  
The Central Nervous System ◽  
Muscle Myosin ◽  
Pro Inflammatory Cytokines

Myosins are a remarkable superfamily of actin-based motor proteins that use the energy derived from ATP hydrolysis to translocate actin filaments and to produce force. Myosins are abundant in different types of tissues and involved in a large variety of cellular functions. Several classes of the myosin superfamily are expressed in the nervous system; among them, non-muscle myosin II (NM II) is expressed in both neurons and non-neuronal brain cells, such as astrocytes, oligodendrocytes, endothelial cells, and microglia. In the nervous system, NM II modulates a variety of functions, such as vesicle transport, phagocytosis, cell migration, cell adhesion and morphology, secretion, transcription, and cytokinesis, as well as playing key roles during brain development, inflammation, repair, and myelination functions. In this review, we will provide a brief overview of recent emerging roles of NM II in resting and activated microglia cells, the principal regulators of immune processes in the central nervous system (CNS) in both physiological and pathological conditions. When stimulated, microglial cells react and produce a number of mediators, such as pro-inflammatory cytokines, free radicals, and nitric oxide, that enhance inflammation and contribute to neurodegenerative diseases. Inhibition of NM II could be a new therapeutic target to treat or to prevent CNS diseases.

scholarly journals Conserved Role of the Large Conductance Calcium-Activated Potassium Channel, KCa1.1, in Sinus Node Function and Arrhythmia Risk

2020 ◽  
Author(s):  
Santiago Pineda ◽  
Vesna Nikolova-Krstevski ◽  
Christiana Leimena ◽  
Andrew J. Atkinson ◽  
Ann-Kristin Altekoester ◽  
...  
Keyword(s):  
Action Potentials ◽  
Ex Vivo ◽  
Sinus Bradycardia ◽  
Sinus Node ◽  
Immunogold Electron Microscopy ◽  
Loss Of Function ◽  
Α Subunit ◽  
Cardiac Functions ◽  
Electrophysiological Characterization

ABSTRACTBackgroundKCNMA1 encodes the α-subunit of the large-conductance Ca2+-activated K+ channel, KCa1.1, and lies within a linkage interval for atrial fibrillation (AF). Insights into the cardiac functions of KCa1.1 are limited and KCNMA1 has not been investigated as an AF candidate gene.Methods and ResultsKCNMA1 sequencing in 118 patients with familial AF identified a novel complex variant in one kindred. To evaluate potential disease mechanisms, we first evaluated the distribution of KCa1.1 in normal hearts using immunostaining and immunogold electron microscopy. KCa1.1 was seen throughout the atria and ventricles in humans and mice, with strong expression in the sinus node. In an ex vivo murine sinoatrial node preparation, addition of the KCa1.1 antagonist, paxilline, blunted the increase in beating rate induced by adrenergic receptor stimulation. Knockdown of the KCa1.1 ortholog, kcnma1b, in zebrafish embryos resulted in sinus bradycardia with dilatation and reduced contraction of the atrium and ventricle. Genetic inactivation of the Drosophila KCa1.1 ortholog, slo, systemically or in adult stages, also slowed the heartbeat and produced cardiac arrhythmias.Electrophysiological characterization of slo-deficient flies revealed bursts of action potentials, reflecting increased events of fibrillatory arrhythmias. Flies with cardiac-specific overexpression of the human KCNMA1 mutant also showed increased heart period and bursts of action potentials, similar to the KCa1.1 loss-of-function models.ConclusionsOur data point to a highly conserved role of KCa1.1 in sinus node function in humans, mice, zebrafish and fly and suggest that KCa1.1 loss of function may predispose to AF.

scholarly journals The role of typology and reactivity in initiation and development of disadaptive disorders

2019 ◽  
pp. 26-34
Author(s):  
А.А. Артеменков
Keyword(s):  
Nervous System ◽  
Mental Disorders ◽  
Transition States ◽  
Mental Activity ◽  
Biological Factors ◽  
Modern Life ◽  
Pathological Conditions

В данном обзоре поднимается проблема переходных состояний, возникающих на грани нормы и патологии, которые принято называть пограничными психическими расстройствами (ППР). В работе высказана гипотеза о том, что в современных условиях жизни человека часто возникает дезинтеграция психической деятельности в связи со значительной информационной нагрузкой на интегративные системы головного мозга. В обобщении материала сделан акцент на описание внутренних (биологических) факторов, определяющих возникновение и развитие дезадаптивных состояний и сопровождающих их пограничных психических расстройств. Обсуждается вопрос о роли индивидуально-типологических свойств нервной системы и реактивности личности в формировании и развитии пограничной психической патологии. Рассматривается вопрос о лечебно-профилактических и коррекционных мероприятиях, направленных на снижение дезадаптивных проявлений у человека в процессе жизнедеятельности и минимизацию пограничных психических расстройств. This review focuses on the issue of transition states that occur on the edge of normal and pathological conditions and are called borderline mental disorders (BMD). The author hypothesized that in the modern life, disintegration of mental activity frequently develops in association with a significant informational load on brain integrative systems. In summarizing the material, an emphasis was made on description of internal (biological) factors that determine the emergence and development of disadaptive conditions and concurrent BMDs. The review discusses the role of individual typological features of the nervous system and individual reactivity in the formation and development of BMD and focuses on therapeutic, preventive, and correctional measures aimed at alleviating disadaptive signs in humans and minimizing BMDs.

Analysis of Heart rate Variability and Implication of Different Factors on Heart Rate Variability

2020 ◽  
Vol 16 ◽  
Author(s):  
Reena Tiwari ◽  
Ravindra Kumar ◽  
Sujata Malik ◽  
Tilak Raj ◽  
Punit Kumar
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Nervous System ◽  
Autonomic Nervous System ◽  
Parasympathetic Nervous System ◽  
Invasive Technique ◽  
Clinical Practices ◽  
Autonomic Nervous ◽  
Pathological Conditions

Background:: The heart is the central organ of the circulatory system which maintains the flow of blood along with the transport of nutrients to different cells and tissues. A well-functioning cardiac state is a complicated mode of changeability. A healthy heart is not only about oscillation as the rhythmometer is not the same in every circumstance. Heart rate shows variations so that it can be regulated according to psychophysiological conditions to maintain the effect of the internal-external stimulus. Objective:: The main objective of this review is to provide a piece of all-inclusive information about heart rate variability (HRV) and different variables affecting HRV. The direct interconnection among factors and so that HRV can be used in clinical practices. Methods:: This review article contains a detailed survey of literature about HRV available in different online sources such as; Google Scholar, Science Direct, PubMed, and Web of Science, etc. In this review, the authors have focused on the role of the autonomic nervous system in the regulation of HRV and the role of various factors affecting HRV. Results:: The variation in the time between two heartbeats is termed as HRV. It is one of the indicators of many pathological conditions related to cardiovascular health. It provided reliable information about the interaction of the sympathetic and parasympathetic nervous systems. The analysis of the variation of heart rate is a well-known non-invasive technique to identify the functioning of the autonomic nervous system. The autonomic nervous system (ANS) depends on the sympathetic and parasympathetic nervous system for transferring information. The cardio-accelerating center, lungs, and non-striated muscles are innervated by cardiac sympathetic nerves. This division of ANS latches upon the heart accordingly via the cervicothoracic ganglion and vagus nerve. It is found that cardiac normal variability depends upon this stimulation towards the sinoatrial node (pacemaker) which can be evaluated by analyzing the HRV. In human- based studies, it has been found that low level of HRV is one of the main causes of death rate among adults. Hence, HRV helps in identifying the risk of cardiac diseases and the state of ANS. Conclusion:: The heart plays a vital role in the human body and the well-functioning of the cardiac system is the need for a healthy life. The heart contains its nervous system termed as neurocardio system in which ANS plays a key role in which the sympathetic and parasympathetic system interplay to regulate HRV. High HRV is associated with healthy condition while low HRV is associated with pathological conditions. The HRV is influenced by various variables such as; pathological, physiological, psychological, environmental factors, lifestyle factors, and genetic factors, etc.

Substitution of extracellular Ca2+ by Sr2+ prolongs inspiratory burst in pre-Bötzinger complex inspiratory neurons

2015 ◽  
Vol 113 (4) ◽  
pp. 1175-1183 ◽  
Author(s):  
Consuelo Morgado-Valle ◽  
Juan Fernandez-Ruiz ◽  
Leonor Lopez-Meraz ◽  
Luis Beltran-Parrazal
Keyword(s):  
Neurotransmitter Release ◽  
Action Potentials ◽  
Hypoglossal Nerve ◽  
Glutamate Release ◽  
Established Method ◽  
Bötzinger Complex ◽  
Inspiratory Activity ◽  
First Time ◽  
Intense Debate

The pre-Bötzinger complex (preBötC) underlies inspiratory rhythm generation. As a result of network interactions, preBötC neurons burst synchronously to produce rhythmic premotor inspiratory activity. Each inspiratory burst consists of action potentials (APs) on top of a 10- to 20-mV synchronous depolarization lasting 0.3–0.8 s known as inspiratory drive potential. The mechanisms underlying the initiation and termination of the inspiratory burst are unclear, and the role of Ca2+ is a matter of intense debate. To investigate the role of extracellular Ca2+ in inspiratory burst initiation and termination, we substituted extracellular Ca2+ with Sr2+. We found for the first time an ionic manipulation that significantly interferes with burst termination. In a rhythmically active slice, we current-clamped preBötC neurons ( Vm ≅ −60 mV) while recording integrated hypoglossal nerve (∫XIIn) activity as motor output. Substitution of extracellular Ca2+ with either 1.5 or 2.5 mM Sr2+ significantly prolonged the duration of inspiratory bursts from 653.4 ± 30.7 ms in control conditions to 981.6 ± 78.5 ms in 1.5 mM Sr2+ and 2,048.2 ± 448.5 ms in 2.5 mM Sr2+, with a concomitant increase in decay time and area. Substitution of extracellular Ca2+ by Sr2+ is a well-established method to desynchronize neurotransmitter release. Our findings suggest that the increase in inspiratory burst duration is determined by a presynaptic mechanism involving desynchronization of glutamate release within the network.

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