scholarly journals Molecular Aspects of Structure, Gating, and Physiology of pH-Sensitive Background K2P and Kir K+-Transport Channels

2015 ◽  
Vol 95 (1) ◽  
pp. 179-217 ◽  
Author(s):  
Francisco V. Sepúlveda ◽  
L. Pablo Cid ◽  
Jacques Teulon ◽  
María Isabel Niemeyer
Keyword(s):  
Animal Studies ◽  
Transepithelial Transport ◽  
Kir Channels ◽  
Functional Studies ◽  
Kir Channel ◽  
Central Chemoreception ◽  
Molecular Aspects ◽  
Transport Channels ◽  
Crucial Part ◽  
The Brain

K+ channels fulfill roles spanning from the control of excitability to the regulation of transepithelial transport. Here we review two groups of K+ channels, pH-regulated K2P channels and the transport group of Kir channels. After considering advances in the molecular aspects of their gating based on structural and functional studies, we examine their participation in certain chosen physiological and pathophysiological scenarios. Crystal structures of K2P and Kir channels reveal rather unique features with important consequences for the gating mechanisms. Important tasks of these channels are discussed in kidney physiology and disease, K+ homeostasis in the brain by Kir channel-equipped glia, and central functions in the hearing mechanism in the inner ear and in acid secretion by parietal cells in the stomach. K2P channels fulfill a crucial part in central chemoreception probably by virtue of their pH sensitivity and are central to adrenal secretion of aldosterone. Finally, some unorthodox behaviors of the selectivity filters of K2P channels might explain their normal and pathological functions. Although a great deal has been learned about structure, molecular details of gating, and physiological functions of K2P and Kir K+-transport channels, this has been only scratching at the surface. More molecular and animal studies are clearly needed to deepen our knowledge.

Inwardly Rectifying Potassium Channels: Their Structure, Function, and Physiological Roles

2010 ◽  
Vol 90 (1) ◽  
pp. 291-366 ◽  
Author(s):  
Hiroshi Hibino ◽  
Atsushi Inanobe ◽  
Kazuharu Furutani ◽  
Shingo Murakami ◽  
Ian Findlay ◽  
...  
Keyword(s):  
Structure Function ◽  
G Protein ◽  
Ion Selectivity ◽  
Inward Rectification ◽  
Transmembrane Helices ◽  
Kir Channels ◽  
Kir Channel ◽  
Transport Channels ◽  
Inwardly Rectifying

Inwardly rectifying K+(Kir) channels allow K+to move more easily into rather than out of the cell. They have diverse physiological functions depending on their type and their location. There are seven Kir channel subfamilies that can be classified into four functional groups: classical Kir channels (Kir2.x) are constitutively active, G protein-gated Kir channels (Kir3.x) are regulated by G protein-coupled receptors, ATP-sensitive K+channels (Kir6.x) are tightly linked to cellular metabolism, and K+transport channels (Kir1.x, Kir4.x, Kir5.x, and Kir7.x). Inward rectification results from pore block by intracellular substances such as Mg2+and polyamines. Kir channel activity can be modulated by ions, phospholipids, and binding proteins. The basic building block of a Kir channel is made up of two transmembrane helices with cytoplasmic NH2and COOH termini and an extracellular loop which folds back to form the pore-lining ion selectivity filter. In vivo, functional Kir channels are composed of four such subunits which are either homo- or heterotetramers. Gene targeting and genetic analysis have linked Kir channel dysfunction to diverse pathologies. The crystal structure of different Kir channels is opening the way to understanding the structure-function relationships of this simple but diverse ion channel family.

scholarly journals (Ascorb)ing Pb Neurotoxicity in the Developing Brain

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1311
Author(s):  
Faraz Ahmad ◽  
Ping Liu
Keyword(s):  
Ascorbic Acid ◽  
Animal Studies ◽  
Redox Homeostasis ◽  
Special Role ◽  
Developmental Exposure ◽  
Brain Functions ◽  
Brain States ◽  
Pb Exposure ◽  
The Brain ◽  
Potent Therapeutic Agent

Lead (Pb) neurotoxicity is a major concern, particularly in children. Developmental exposure to Pb can alter neurodevelopmental trajectory and has permanent neuropathological consequences, including an increased vulnerability to further stressors. Ascorbic acid is among most researched antioxidant nutrients and has a special role in maintaining redox homeostasis in physiological and physio-pathological brain states. Furthermore, because of its capacity to chelate metal ions, ascorbic acid may particularly serve as a potent therapeutic agent in Pb poisoning. The present review first discusses the major consequences of Pb exposure in children and then proceeds to present evidence from human and animal studies for ascorbic acid as an efficient ameliorative supplemental nutrient in Pb poisoning, with a particular focus on developmental Pb neurotoxicity. In doing so, it is hoped that there is a revitalization for further research on understanding the brain functions of this essential, safe, and readily available vitamin in physiological states, as well to justify and establish it as an effective neuroprotective and modulatory factor in the pathologies of the nervous system, including developmental neuropathologies.

scholarly journals Remote control of neural function by X-ray-induced scintillation

2019 ◽  
Author(s):  
Takanori Matsubara ◽  
Takayuki Yanagida ◽  
Noriaki Kawaguchi ◽  
Takashi Nakano ◽  
Junichiro Yoshimoto ◽  
...  
Keyword(s):  
Dopamine Neurons ◽  
Neural Function ◽  
X Rays ◽  
Cellular Functions ◽  
X Ray ◽  
Functional Studies ◽  
Clinical Dose ◽  
Visible Luminescence ◽  
Midbrain Dopamine ◽  
The Brain

Scintillators emit visible luminescence when irradiated with X-rays. Given the unlimited tissue penetration of X-rays, the employment of scintillators could enable remote optogenetic control of neural functions at any depth of the brain. Here we show that a yellow-emitting inorganic scintillator, Ce-doped Gd3(Al,Ga)5O12 (Ce:GAGG), could effectively activate red-shifted excitatory and inhibitory opsins, ChRmine and GtACR1, respectively. Using injectable Ce:GAGG microparticles, we successfully activated and inhibited midbrain dopamine neurons in freely moving mice by X-ray irradiation, producing bidirectional modulation of place preference behavior. Ce:GAGG microparticles were non-cytotoxic and biocompatible, allowing for chronic implantation. Pulsed X-ray irradiation at a clinical dose level was sufficient to elicit behavioral changes without reducing the number of radiosensitive cells in the brain and bone marrow. Thus, scintillator-mediated optogenetics enables less invasive, wireless control of cellular functions at any tissue depth in living animals, expanding X-ray applications to functional studies of biology and medicine.

scholarly journals A neuroscientific grasp of concepts: from control to representation

2003 ◽  
Vol 358 (1435) ◽  
pp. 1231-1240 ◽  
Author(s):  
Vittorio Gallese
Keyword(s):  
Conceptual Knowledge ◽  
Outer Space ◽  
Cognitive Activity ◽  
Semantic Content ◽  
Macaque Monkey ◽  
Conceptual Representations ◽  
Neurophysiological Data ◽  
Neural Underpinnings ◽  
Crucial Part ◽  
The Brain

Abstraction denotes the cognitive process by means of which general concepts are formed. The dominant view of abstraction considers it not only as a complex and sophisticated cognitive activity, but also as a distinctive hallmark of mankind. The distinctiveness of abstract thought has indeed been closely related to another feature peculiar to our species: language. Following this perspective, the possibility to entertain conceptual representations is thus precluded to animals devoid of full–blown language. I challenge this view and propose that the representational dynamic of the brain is conceivable as a type of self–organization, in which action plays a crucial part. My aim will be to investigate whether, and to what extent, conceptual knowledge can be attributed to non–linguistic animal species, with particular emphasis on nonhuman primates. I therefore introduce the notion of semantic content as a type of ‘relational specification’. A review of recent neurophysiological data on the neural underpinnings of action end–states in the macaque monkey brain is presented. On the basis of this evidence, I propose that conceptual representations can be conceived as the expression of a coherent internal world model. This model decomposes the ‘outer’ space inhabited by things in a meaningful way only to the extent that it accords to biologically constrained, embodied invariance. Finally, I discuss how the ‘comparative’ neuroscientific approach to abstraction proposed here may shed some light on its nature and its evolutionary origin.

Babies and bathwaters: attachment, neuroscience, evolution and the left

Soundings ◽  
2019 ◽  
Vol 73 (73) ◽  
pp. 111-128
Author(s):  
Graham Music
Keyword(s):  
Attachment Theory ◽  
Developmental Psychology ◽  
Huge Amount ◽  
Far Right ◽  
Interpersonal Neurobiology ◽  
Selfish Genes ◽  
The Social ◽  
Social Orders ◽  
Crucial Part ◽  
The Brain

This article challenges thinkers and activists on the left who are over-suspicious of ideas heralding from disciplines such as interpersonal neurobiology, attachment theory, developmental psychology, and perhaps especially, evolutionary theory. Although scepticism is frequently warranted, especially as such discourses are often co-opted for neoliberal or far right ends, there is much in all of them that melds well with critiques of hegemonic social orders, providing potential fuel for those working for social change. Much work, for example that of Amy Cuddy, can be interpreted both conservatively and progressively. Work from within an attachment theory paradigm can play a crucial part in the battle of ideas: it has a huge amount to teach about how to create a more humane and egalitarian world, and in countering neoliberal beliefs that humans are innately primarily aggressive, competitive or selfish, or have selfish genes. The days are now over when the biological, psychological and the social need to be pitted against each other. Rather, they now have to be seen as mutually constituted. The brain is a social organ, embedded, embodied, enactive and extended, in large part a reflection of the social conditions in which it grows.

Brain Development and the Risk for Substance Abuse

2013 ◽  
pp. 706-715
Author(s):  
Kristina Caudle ◽  
B.J. Casey
Keyword(s):  
Substance Abuse ◽  
Substance Use ◽  
Brain Development ◽  
Substance Use Disorders ◽  
Animal Studies ◽  
Substance Abuse Problem ◽  
Increased Risk ◽  
Drug And Alcohol ◽  
The Brain ◽  
Developmental Window

Drug and alcohol dependence affects millions each year. Adolescence is a period of increased risk for substance use disorders. Understanding how the brain is changing during this developmental window relative to childhood and adulthood and how these changes vary across individuals is critical for predicting risk of later substance abuse and dependence. This chapter provides an overview of recent human imaging and animal studies of brain development focusing on changes in corticostriatal circuitry that has been implicated in addiction. Behavioral, clinical, and neurobiological evidence is provided to help elucidate who may be most at risk for developing a substance abuse problem and whenthey may be most vulnerable.

scholarly journals Vestibular implants studied in animal models: clinical and scientific implications

2016 ◽  
Vol 116 (6) ◽  
pp. 2777-2788 ◽  
Author(s):  
Richard F. Lewis
Keyword(s):  
Animal Models ◽  
Vestibular System ◽  
Animal Studies ◽  
Vestibular Function ◽  
Clinical Problem ◽  
Head Motion ◽  
The Past ◽  
New Treatment ◽  
Vestibular Damage ◽  
The Brain

Damage to the peripheral vestibular system can result in debilitating postural, perceptual, and visual symptoms. A potential new treatment for this clinical problem is to replace some aspects of peripheral vestibular function with an implant that senses head motion and provides this information to the brain by stimulating branches of the vestibular nerve. In this review I consider animal studies performed at our institution over the past 15 years, which have helped elucidate how the brain processes information provided by a vestibular (semicircular canal) implant and how this information could be used to improve the problems experienced by patients with peripheral vestibular damage.

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