The role of K-channels in the formation of a nociceptive signal in the rat trigeminal nerve

2021 ◽  
Author(s):  
A.D. Buglinina ◽  
T.M. Verkhoturova ◽  
O.Sh. Gafurov ◽  
K.S. Koroleva ◽  
G.F. Sitdikova
Keyword(s):  
Key Words ◽  
Trigeminal Nerve ◽  
Key Words Migraine ◽  
K Channels ◽  
Kv Channel ◽  
Inflammatory Agent ◽  
Kv Channels ◽  
Pain Signal ◽  
Isolated Rat

The central problem of this work is to elucidate the mechanisms of pain in migraine and to establish the role of Kv channels in regulating the excitability of meningeal afferents of the trigeminal nerve that form a pain signal in migraine. The study was conducted on a preparation of an isolated rat skull. It was found that Kv-channel inhibitors 4-aminopyridine (100 microns and 1 mM) and tetraethylammonium (5mm) lead to an increase in the excitability of trigeminal nerve afferents, at the same time, this effect was partially removed by a nonsteroidal anti–inflammatory agent - naproxen, and was not sensitive to sumatriptan, a classic anti-migraine drug. Key words: migraine, K-channels, trigeminal nerve, 4-aminopyridine, tetraethylammonium, naproxen, sumatriptan.

Role of K+Channels in Augmented Relaxations to Sodium Nitroprusside Induced by Mexiletine in Rat Aortas

2000 ◽  
Vol 92 (3) ◽  
pp. 813-820 ◽  
Author(s):  
Hiroyuki Kinoshita ◽  
Toshizo Ishikawa ◽  
Yoshio Hatano
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Sodium Nitroprusside ◽  
Guanylate Cyclase ◽  
Nitric Oxide Donor ◽  
Nitric Oxide Donors ◽  
K Channels ◽  
Vasodilator Effect ◽  
Isolated Rat

Background A class Ib antiarrhythmic drug, mexiletine, augments relaxations produced by adenosine triphosphate (ATP) sensitive K+ channel openers in isolated rat aortas, suggesting that it produces changes in the vasodilation mediated by ATP-sensitive K+ channels. Nitric oxide can induce its vasodilator effect via K+ channels, including ATP-sensitive K+ channels, in smooth muscle cells. Effects of mexiletine on arterial relaxations to nitric oxide donors, have not been studied. Therefore, the current study in isolated rat aortas was designed to (1) evaluate whether mexiletine augments relaxation in response to nitric oxide donors, including sodium nitroprusside, and (2) determine the role of K+ channels in mediating effects of mexiletine on such nitric oxide-mediated relaxation. Methods Rings of rat aortas without endothelia were suspended for isometric force recording. Concentration-response curves of sodium nitroprusside (10(-10) to 10(-5) M) and 1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7; 10(-9) to 10(-5) M) were obtained in the absence and in the presence of mexiletine, in combination with a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo [4,3,-a]quinoxaline-1-one (ODQ), or inhibitors for ATP-sensitive K+ channels (glibenclamide), inward rectifier K+ channels (BaCl2), delayed rectifier K+ channels (4-aminopyridine), large conductance Ca2+-dependent K+ channels (iberiotoxin), or small conductance Ca2+-dependent K+ channels (apamin). Results Mexiletine (10(-5) or 3 x 10(-5) M) augmented relaxations to sodium nitroprusside and NOC-7. In arteries treated with glibenclamide (10(-5) M), mexiletine (3 x 10(-5) M) did not affect relaxations to nitric oxide donors, whereas mexiletine augmented relaxations to sodium nitroprusside despite the presence of BaCl2 (10(-5) M), 4-aminopyridine (10(-3) M), iberiotoxin (5 x 10(-8) M) and apamin (5 x 10(-8) M). Relaxations to sodium nitroprusside were abolished by ODQ (5 x 10(-6) M), whereas these relaxations were augmented by mexiletine (3 x 10(-5) M) in arteries treated with ODQ (5 x 10(-6) M). Conclusions These results suggest that ATP-sensitive K+ channels in vascular smooth muscle, contribute to the augmented vasodilator effect of a nitric oxide donor, sodium nitroprusside induced by mexiletine, and that the vasodilator effect is produced, at least in part, via the guanylate cyclase-independent mechanism.

scholarly journals Constitutive Activation of the Shaker Kv Channel

2003 ◽  
Vol 122 (5) ◽  
pp. 541-556 ◽  
Author(s):  
Manana Sukhareva ◽  
David H. Hackos ◽  
Kenton J. Swartz
Keyword(s):  
Single Channel ◽  
Membrane Depolarization ◽  
Ion Conduction ◽  
K Channels ◽  
Voltage Sensors ◽  
Kv Channel ◽  
Kv Channels ◽  
Activation Gate ◽  
Sensor Activation ◽  
Primary Activation

In different types of K+ channels the primary activation gate is thought to reside near the intracellular entrance to the ion conduction pore. In the Shaker Kv channel the gate is closed at negative membrane voltages, but can be opened with membrane depolarization. In a previous study of the S6 activation gate in Shaker (Hackos, D.H., T.H. Chang, and K.J. Swartz. 2002. J. Gen. Physiol. 119:521–532.), we found that mutation of Pro 475 to Asp results in a channel that displays a large macroscopic conductance at negative membrane voltages, with only small increases in conductance with membrane depolarization. In the present study we explore the mechanism underlying this constitutively conducting phenotype using both macroscopic and single-channel recordings, and probes that interact with the voltage sensors or the intracellular entrance to the ion conduction pore. Our results suggest that constitutive conduction results from a dramatic perturbation of the closed-open equilibrium, enabling opening of the activation gate without voltage-sensor activation. This mechanism is discussed in the context of allosteric models for activation of Kv channels and what is known about the structure of this critical region in K+ channels.

scholarly journals Ancillary Subunits Associated With Voltage-Dependent K+ Channels

2010 ◽  
Vol 90 (2) ◽  
pp. 755-796 ◽  
Author(s):  
Olaf Pongs ◽  
Jürgen R. Schwarz
Keyword(s):  
Enzymatic Activity ◽  
Physiological Role ◽  
Structural Diversity ◽  
Periodic Paralysis ◽  
Β Subunit ◽  
Kv Channel ◽  
Kv Channels ◽  
Channel Assembly

Since the first discovery of Kvβ-subunits more than 15 years ago, many more ancillary Kv channel subunits were characterized, for example, KChIPs, KCNEs, and BKβ-subunits. The ancillary subunits are often integral parts of native Kv channels, which, therefore, are mostly multiprotein complexes composed of voltage-sensing and pore-forming Kvα-subunits and of ancillary or β-subunits. Apparently, Kv channels need the ancillary subunits to fulfill their many different cell physiological roles. This is reflected by the large structural diversity observed with ancillary subunit structures. They range from proteins with transmembrane segments and extracellular domains to purely cytoplasmic proteins. Ancillary subunits modulate Kv channel gating but can also have a great impact on channel assembly, on channel trafficking to and from the cellular surface, and on targeting Kv channels to different cellular compartments. The importance of the role of accessory subunits is further emphasized by the number of mutations that are associated in both humans and animals with diseases like hypertension, epilepsy, arrhythmogenesis, periodic paralysis, and hypothyroidism. Interestingly, several ancillary subunits have in vitro enzymatic activity; for example, Kvβ-subunits are oxidoreductases, or modulate enzymatic activity, i.e., KChIP3 modulates presenilin activity. Thus different modes of β-subunit association and of functional impact on Kv channels can be delineated, making it difficult to extract common principles underlying Kvα- and β-subunit interactions. We critically review present knowledge on the physiological role of ancillary Kv channel subunits and their effects on Kv channel properties.

Kv2 channels oppose myogenic constriction of rat cerebral arteries

2006 ◽  
Vol 291 (2) ◽  
pp. C348-C356 ◽  
Author(s):  
Gregory C. Amberg ◽  
Luis F. Santana
Keyword(s):  
Smooth Muscle ◽  
Calcium Influx ◽  
Cerebral Arteries ◽  
Specific Inhibitor ◽  
Arterial Smooth Muscle ◽  
Membrane Hyperpolarization ◽  
Kv Channel ◽  
Channel Function ◽  
Kv Channels

By hyperpolarizing arterial smooth muscle, voltage-gated, Ca2+-independent K+ (Kv) channels decrease calcium influx and thus oppose constriction. However, the molecular nature of the Kv channels function in arterial smooth muscle remains controversial. Recent investigations have emphasized a predominant role of Kv1 channels in regulating arterial tone. In this study, we tested the hypothesis Kv2 channels may also significantly regulate tone of rat cerebral arteries. We found that Kv2.1 transcript and protein are present in cerebral arterial smooth muscle. In addition, our analysis indicates that a substantial component (≈50%) of the voltage dependencies and kinetics of Kv currents in voltage-clamped cerebral arterial myocytes is consistent with Kv2 channels. Accordingly, we found that stromatoxin, a specific inhibitor of Kv2 channels, significantly decreased Kv currents in these cells. Furthermore, stromatoxin enhanced myogenic constriction of pressurized arterial segments. We also found that during angiotensin II-induced hypertension, Kv2 channel function was reduced in isolated myocytes and in intact arteries. This suggests that impaired Kv2 channel activity may contribute to arterial dysfunction during hypertension. On the basis of these novel observations, we propose a new model of Kv channel function in arterial smooth muscle in which Kv2 channels (in combination with Kv1 channels) contribute to membrane hyperpolarization and thus oppose constriction.

THE ROLE OF COMMUNICATIVE AND FUNCTIONAL APPROACH IN THE TRANSLATION OF SCIENTIFIC AND TECHNICAL LITERATURE (Ukrainian — German discourse)

2019 ◽  
Vol 26 (27) ◽  
pp. 68-74
Author(s):  
Svitlana Gruschko
Keyword(s):  
Key Words ◽  
Information Exchange ◽  
Functional Approach ◽  
Communication Structure ◽  
Technical Literature ◽  
Translation Strategy ◽  
Purposeful Activity

The article investigates the role of communicative-functional approach in the translation of scientific and technical literature, when the translation itself is seen as a tool to accomplish purposeful activity of communicators, representatives of different interlingual groups. In practical terms, the difficulties of translating scientific and technical texts are due to the peculiarities of scientific style, insufficient understanding of the terminology of a particular field of knowledge, which complicates the choice of adequate translation solutions. In this context, an important role is played by the translation strategy, where the communicativefunctional approach dominates. The translation is implicitly included in the communication structure between the author and the recipient. The relevance of the article is determined by the necessity of studying the problems of scientific and technical literature translation, taking into account the current realities of interlanguage information exchange. Key words: communicative-functional approach, interlingual communication, translation, structure

INTERPRETATIONAL FIELD OF THE CONCEPT “WOMAN” IN ENGLISH AND KYRGYZ LINGUOCULTURES

2019 ◽  
pp. 54-56
Author(s):  
Баяманова М.С.
Keyword(s):  
Comparative Study ◽  
Key Words ◽  
Analytical Data ◽  
Semantic Field ◽  
Traditional Values ◽  
Lexical Unit ◽  
Semantic Fields ◽  
Field Culture

Summary: The article deals with the analysis of the interpretational field of the basic lexical units which represent the meaning of the concept “woman” in English and Kyrgyz languages and cultures. Comparative – contrastive analytical data of the most frequently used in both languages variants of the interpretation of the concept “woman” have been given. The semantic fields of nuclear and nearnuclear meanings of the lexical units, transforming the notion of “woman” in English and Kyrgyz languages and also the place and role of these notions in cultures and philosophy of the nations on the basis of mentality and traditional values have been studied and described. The situations of the use of this or that variant of the meaning of lexical unit. A comparative study of the definitions of the word “woman’ in English and Kyrgyz languages have been given. Key words: concept, woman, interpretational field, notion, definition, semantic field, culture, language, linguoculture, transformation Аннотация: В статье рассматриваются интерпретационные поля основных лексических единиц, репрезентирующих значение концепта «женщина» в английской и кыргызской лингвокультурах. Приводятся сравнительно-сопоставительные аналитические данные наиболее употребительных в речи обоих языков вариантов интерпретации концепта «женщина». Изучены и описаны семантические поля ядерных и околоядерных значений лексических единиц, трансформирующих понятие «женщина» в английском и кыргызском языке, а также роль и место этих понятий в культурах и философии народов на основе менталитета и традиционных ценностей. Приводятся ситуации использования того или ино- го варианта значения лексической единицы, проведено сравнительное изучение определений слова «женщина» в английском и кыргызском языках. Ключевые слова: концепт, женщина, интерпретационное поле, понятие, определение, семантическое поле, культура, язык, лингвокультура, трансформация Аннотация: Макалада англис жана кыргыз тилдеринде жана маданияттарында «аял» концептинин маанисин репрезентациалаган негизги лексикалык бирдиктер каралат. «Аял» концептин эки тилдеги кѳп колдонулуучу интерпретациялоо варианттарынын аналитикалык салыштырма маалыматтары изил- делип берилген. Англис жана кыргыз тилдеринде «аял» түшүнүгүн трансформациялаган лексикалык бирдиктердин түп нуска жана ага жакындашкан маанилери иликтелип каралган. Берилген түшүнүктѳрдүн элдик философиясында жана маданиятында, менталитеттин жана салттын негизинде эл арасына кеӊири тараган, элдик тилде жана маданиятта ойногон ролу менен орду чагылдырылган. Ар түрдү ситацияларда колдонулуучу тиги же бул лексикалык бирдиктердин маанисинин варианттары каралган, «аял» деген сѳздун англис жана кыргыз тилдериндеги түшүндүрмѳлѳрү салыштырылып изилделген. Түйүндүү сѳздѳр: концепт, аял, интерпретациялоо мейкиндиги, түшүнүк, түшүндүрмѳ, семантикалык чѳйрѳ, маданият, тил, лингвомаданият, трансформациялоо

Enhanced role of K+ channels in relaxations of hypercholesterolemic rabbit carotid artery to NO

1995 ◽  
Vol 269 (3) ◽  
pp. H805-H811 ◽  
Author(s):  
S. Najibi ◽  
R. A. Cohen
Keyword(s):  
Carotid Artery ◽  
Sodium Nitroprusside ◽  
Channel Blocker ◽  
Isometric Tension ◽  
K Channel ◽  
K Channels ◽  
Rabbit Carotid Artery ◽  
Cyclic Monophosphate ◽  
Endothelium Dependent Relaxation

Endothelium-dependent relaxations to acetylcholine remain normal in the carotid artery of hypercholesterolemic rabbits, but unlike endothelium-dependent relaxations of normal rabbits, they are inhibited by charybdotoxin, a specific blocker of Ca(2+)-dependent K+ channels. Because nitric oxide (NO) is the mediator of endothelium-dependent relaxation and can activate Ca(2+)-dependent K+ channels directly or via guanosine 3',5'-cyclic monophosphate, the present study investigated the role of Ca(2+)-dependent K+ channels in relaxations caused by NO, sodium nitroprusside, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-Brc-GMP) in hypercholesterolemic rabbit carotid artery. Isometric tension was measured in rabbit carotid artery denuded of endothelium from normal and hypercholesterolemic rabbits which were fed 0.5% cholesterol for 12 wk. Under control conditions, relaxations to all agents were similar in normal and hypercholesterolemic rabbit arteries. Charybdotoxin had no significant effect on relaxations of normal arteries to NO, sodium nitroprusside, or 8-BrcGMP, but the Ca(2+)-dependent K+ channel blocker significantly inhibited the relaxations caused by each of these agents in the arteries from hypercholesterolemic rabbits. By contrast, relaxations to the calcium channel blocker nifedipine were potentiated to a similar extent by charybdotoxin in both groups. In addition, arteries from hypercholesterolemic rabbits relaxed less than normal to sodium nitroprusside when contracted with depolarizing potassium solution. These results indicate that although nitrovasodilator relaxations are normal in the hypercholesterolemic rabbit carotid artery, they are mediated differently, and to a greater extent, by Ca(2+)-dependent K+ channels. These data also suggest that K+ channel-independent mechanism(s) are impaired in hypercholesterolemia.

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