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1.
J. venom. anim. toxins incl. trop. dis ; J. venom. anim. toxins incl. trop. dis;30: e20230048, 2024. tab, graf
Article de Anglais | LILACS-Express | LILACS, VETINDEX | ID: biblio-1575194

RÉSUMÉ

Abstract The effect of peptide toxins on voltage-gated ion channels can be reliably assessed using electrophysiological assays, such as the patch-clamp technique. However, much of the toxinological research done in Central and South America aims at purifying and characterizing biochemical properties of the toxins of vegetal or animal origin, lacking electrophysiological approaches. This may happen due to technical and infrastructure limitations or because researchers are unfamiliar with the techniques and cellular models that can be used to gain information about the effect of a molecule on ion channels. Given the potential interest of many research groups in the highly biodiverse region of Central and South America, we reviewed the most relevant conceptual and methodological developments required to implement the evaluation of the effect of peptide toxins on mammalian voltage-gated ion channels using patch-clamp. For that, we searched MEDLINE/PubMed and SciELO databases with different combinations of these descriptors: "electrophysiology", "patch-clamp techniques", "Ca2+ channels", "K+ channels", "cnidarian venoms", "cone snail venoms", "scorpion venoms", "spider venoms", "snake venoms", "cardiac myocytes", "dorsal root ganglia", and summarized the literature as a scoping review. First, we present the basics and recent advances in mammalian voltage-gated ion channel's structure and function and update the most important animal sources of channel-modulating toxins (e.g. cnidarian and cone snails, scorpions, spiders, and snakes), highlighting the properties of toxins electrophysiologically characterized in Central and South America. Finally, we describe the local experience in implementing the patch-clamp technique using two models of excitable cells, as well as the participation in characterizing new modulators of ion channels derived from the venom of a local spider, a toxins' source less studied with electrophysiological techniques. Fostering the implementation of electrophysiological methods in more laboratories in the region will strengthen our capabilities in many fields, such as toxinology, toxicology, pharmacology, natural products, biophysics, biomedicine, and bioengineering.

2.
Indian J Physiol Pharmacol ; 2023 Mar; 67(1): 57-63
Article | IMSEAR | ID: sea-223979

RÉSUMÉ

Objectives: Centrally-acting antitussives with inhibitory effects on G protein-coupled inwardly rectifying potassium (GIRK) channels have been shown to also inhibit methamphetamine-induced hyperactivity in mice. In this study, we examined if cloperastine, which is the most potent inhibitor of the GIRK channels among antitussives, is sensitive to the expression levels of GIRK channels in the brain of methamphetaminetreated mice. Materials and Methods: The brain tissues have been removed and the total RNA has been extracted from tissues. The mRNA levels were evaluated using semiquantitative reverse transcription-polymerase chain reaction. Results: The concentration levels of the mRNA of GIRK channels within the ventral midbrain of methamphetamine-treated mice increased as compared with that in control and cloperastine reduced an upregulation in GIRK2, one of the subunits of the GIRK channels, by the injection of methamphetamine. Conclusion: These findings suggest that cloperastine might ameliorate hyperactivity by inhibiting the GIRK channels in the brain.

3.
J. biomed. eng ; Sheng wu yi xue gong cheng xue za zhi;(6): 8-19, 2023.
Article de Chinois | WPRIM | ID: wpr-970668

RÉSUMÉ

Weightlessness in the space environment affects astronauts' learning memory and cognitive function. Repetitive transcranial magnetic stimulation has been shown to be effective in improving cognitive dysfunction. In this study, we investigated the effects of repetitive transcranial magnetic stimulation on neural excitability and ion channels in simulated weightlessness mice from a neurophysiological perspective. Young C57 mice were divided into control, hindlimb unloading and magnetic stimulation groups. The mice in the hindlimb unloading and magnetic stimulation groups were treated with hindlimb unloading for 14 days to establish a simulated weightlessness model, while the mice in the magnetic stimulation group were subjected to 14 days of repetitive transcranial magnetic stimulation. Using isolated brain slice patch clamp experiments, the relevant indexes of action potential and the kinetic property changes of voltage-gated sodium and potassium channels were detected to analyze the excitability of neurons and their ion channel mechanisms. The results showed that the behavioral cognitive ability and neuronal excitability of the mice decreased significantly with hindlimb unloading. Repetitive transcranial magnetic stimulation could significantly improve the cognitive impairment and neuroelectrophysiological indexes of the hindlimb unloading mice. Repetitive transcranial magnetic stimulation may change the activation, inactivation and reactivation process of sodium and potassium ion channels by promoting sodium ion outflow and inhibiting potassium ion, and affect the dynamic characteristics of ion channels, so as to enhance the excitability of single neurons and improve the cognitive damage and spatial memory ability of hindlimb unloading mice.


Sujet(s)
Animaux , Souris , Stimulation magnétique transcrânienne , Suspension des membres postérieurs , Neurones , Dysfonctionnement cognitif , Encéphale
4.
Chinese Journal of Neurology ; (12): 269-277, 2023.
Article de Chinois | WPRIM | ID: wpr-994827

RÉSUMÉ

Objective:To investigate the clinical characteristics and outcome of patients with voltage-gated potassium channel complex (VGKCc) antibody associated clinical syndromes complicated with myasthenia gravis (MG) with thymoma.Methods:The clinical history, examinations and follow-up prognosis of 2 cases of VGKCc antibodies associated clinical syndromes with MG complicated with thymoma in Qilu Hospital (Qingdao), Cheeloo College of Medicine,Shandong University in September 2020 and December 2020 were reviewed. Related literatures were summarized at the same time.Results:Case 1, a 64-year-old female clinically presented with cognitive impairment, psychosis, and epilepsy seizures, whose serum autoimmune antibody testing showed positive leucine-rich glioma-inhibited 1 (LGI1) antibody, was diagnosed as anti-LGI1 encephalitis,and had history of MG with thymoma. Her symptoms were improved by immunotherapy. Case 2, a 67-year-old male, was diagnosed as MG, and developed cognitive impairment, myokymia and autonomic dysfunction later. His serum autoimmune antibody testing showed positive contactin associated protein-like 2 antibody. Therefore, Morvan syndrome complicated with MG with thymoma was definitely diagnosed. After admission, the patient was improved with immunotherapy and thymoma resection.Conclusions:Patients with VGKCc antibody-associated clinical syndromes complicated with MG have the clinical characteristics of the two diseases simultaneously, and there is also crossover. Immunotherapy and treatment for thymoma are generally effective.

5.
Chinese Pharmacological Bulletin ; (12): 1068-1073, 2023.
Article de Chinois | WPRIM | ID: wpr-1013899

RÉSUMÉ

Aim To analyze the genotype-phenotype characteristics of voltage-gated potassium channels (Kv) associated genetic epilepsy and evaluate the efficacy of anti-seizure medications(ASMs). Methods PubMed database was searched and patients meeting the inclusion criteria were included for analysis. We divided the patients into “benign”, “encephalopathic” and other phenotypes according to the clinical characteristics. We performed descriptive statistical analysis of patients' mutated genes, clinical phenotype and drug efficacy, and used logistic regression to explore the influencing factors of treatment outcome. Results Data of 474 children were included for analysis. There were significant differences among different phenotypes in mutated genes, source of mutations and so on. In terms of clinical characteristics, there were also significant differences between patients with different phenotypes in age of onset, combined developmental delay and so on. In terms of monotherapy, phenobarbital was the most common treatment choice for children with “benign” phenotype, and sodium channel blockers (SCBs) were the most common treatment choice for children with “encephalopathy” phenotype, and the efficacy of SCBs monotherapy was superior to that of other ASMs. Multivariate Logistic analysis of the children receiving monotherapy showed that whether the children were combined with developmental delay and whether SCBs were used were significant factors influencing the efficacy of drug therapy. Conclusions Patients with the “benign” and “encephalopathic” phenotypes differ in several aspects of genetic variation, clinical characteristics, and drug selection. These results suggest that SCBs may be one of the recommended options for monotherapy.

6.
Chinese Journal of Biotechnology ; (12): 3695-3709, 2023.
Article de Chinois | WPRIM | ID: wpr-1007986

RÉSUMÉ

Uridine is one of the essential nutrients in organisms. To maintain normal cell growth and intracellular metabolism, the uridine must be maintained at certain concentration. Recent studies have shown that uridine can reduce inflammatory response in organisms, participate in glycolysis, and regulate intracellular protein modification, such as glycosylation and acetylation. Furthermore, it can protect cells from hypoxic injury by reducing intracellular oxidative stress, promoting high-energy compounds synthesis. Previous studies have shown that the protective effects of uridine are closely related to its effect on mitochondria. This review summarizes the effect of uridine on mitochondrial function.


Sujet(s)
Uridine/métabolisme , Mitochondries/métabolisme
7.
Chinese Journal of Pathophysiology ; (12): 2113-2122, 2023.
Article de Chinois | WPRIM | ID: wpr-1023819

RÉSUMÉ

AIM:To explore the modulation of 2-arachidonoylglycerol(2-AG)on A-type potassium channels injured by kainic acid(KA)and its molecular mechanism.METHODS:Primary cultured caudate nucleus(CN)neurons were treated with KA to establish a neuroexcitatory toxicity model.Whole-cell patch clamp recording was performed to ob-serve the changes of electrical activity of A-type potassium channels induced by KA-induced excitatory toxicity and 2-AG-mediated neuroprotective effect.RESULTS:In cultured CN neurons,patch clamp experiments confirmed that KA signifi-cantly decreased the A-type potassium channel current(IA)density and changed the electrical function of CN neurons:the slope(k)of inactivation curve and the recovery time constant(τ)after inactivation of A-type potassium channels in CN neurons were significantly increased.The experiments showed that the increase in 2-AG level,whether using 2-AG direct-ly or application of monoacylglycerol lipase inhibitor URB602 to decrease 2-AG metabolism and increase 2-AG level indi-rectly,inhibited the KA-induced reduction of IA density and the changes of electrical activity of A-type potassium channels through cannabinoid receptor 1(CB1R):2-AG effectively antagonized the KA-induced increases in τ value and k value for inactivation of A-type potassium channels,which accelerated the recovery process after inactivation of the channels.CONCLUSION:The changes of the electrical characteristics of A-type potassium channels may be one of the mecha-nisms of KA-induced excitotoxic injury of CN neurons.The 2-AG plays a neuroprotective role in KA-induced neuroexcit-atory toxic model by regulating the function of A-type potassium channels through CB1R.

8.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;56: e12392, 2023. graf
Article de Anglais | LILACS-Express | LILACS | ID: biblio-1420750

RÉSUMÉ

Distal convoluted tubules (DCT), which contain the Na-Cl cotransporter (NCC) inhibited by thiazide diuretics, undergo complex modulation to preserve Na+ and K+ homeostasis. The lysine kinases 1 and 4 (WNK1 and WNK4), identified as hyperactive in the hereditary disease pseudohypoaldosteronism type 2, are responsible for activation of NCC and consequent hypokalemia and hypertension. WNK4, highly expressed in DCT, activates the SPAK/OSR1 kinases, which phosphorylate NCC and other regulatory proteins and transporters in the distal nephron. WNK4 works as a chloride sensor through a Cl- binding site, which acts as an on/off switch at this kinase in response to changes of basolateral membrane electrical potential, the driving force of cellular Cl- efflux. High intracellular Cl- in hyperkalemia decreases NCC phosphorylation and low intracellular Cl- in hypokalemia increases NCC phosphorylation and activity, which makes plasma K+ concentration a central modulator of NCC and of K+ secretion. The WNK4 phosphorylation by cSrc or SGK1, activated by angiotensin II or aldosterone, respectively, is another relevant mechanism of NCC, ENaC, and ROMK modulation in states such as volume reduction, hyperkalemia, and hypokalemia. Loss of NCC function induces upregulation of electroneutral NaCl reabsorption by type B intercalated cells through the combined activity of pendrin and NDCBE, as demonstrated in double knockout mice (KO) animal models, Ncc/pendrin or Ncc/NDCBE. The analysis of ks-Nedd-4-2 KO animal models introduced the modulation of NEDD4-2 by intracellular Mg2+ activity as an important regulator of NCC, explaining the thiazide-induced persistent hypokalemia.

9.
Acta Pharmaceutica Sinica B ; (6): 665-677, 2022.
Article de Anglais | WPRIM | ID: wpr-929318

RÉSUMÉ

Sulfonylureas are widely used oral anti-diabetic drugs. However, its long-term usage effects on patients' lifespan remain controversial, with no reports of influence on animal longevity. Hence, the anti-aging effects of chlorpropamide along with glimepiride, glibenclamide, and tolbutamide were studied with special emphasis on the interaction of chlorpropamide with mitochondrial ATP-sensitive K+ (mitoK-ATP) channels and mitochondrial complex II. Chlorpropamide delayed aging in Caenorhabditis elegans, human lung fibroblast MRC-5 cells and reduced doxorubicin-induced senescence in both MRC-5 cells and mice. In addition, the mitochondrial membrane potential and ATP levels were significantly increased in chlorpropamide-treated worms, which is consistent with the function of its reported targets, mitoK-ATP channels. Increased levels of mitochondrial reactive oxygen species (mtROS) were observed in chlorpropamide-treated worms. Moreover, the lifespan extension by chlorpropamide required complex II and increased mtROS levels, indicating that chlorpropamide acts on complex II directly or indirectly via mitoK-ATP to increase the production of mtROS as a pro-longevity signal. This study provides mechanistic insight into the anti-aging effects of sulfonylureas in C. elegans.

10.
Article de Chinois | WPRIM | ID: wpr-931276

RÉSUMÉ

Objective:To analyze clinical characteristics and genetic characteristics of children with ATP sensitive potassium passage (K ATP-HI). Methods:Forty-five children with genetically confirmed K ATP-HI and their families admitted to Beijing Children′s Hospital of Capital Medical University between February 2002 and December 2018 were selected as the study subjects. A detailed retrospective analysis of the patient's clinical characteristics, diagnosis and treatment process, disease-causing gene carrying status and later follow-up data was performed. ABCC8/KCNJ11 gene was sequenced by second-generation sequencing technology. Results:Among 45 children with K ATP-HI, 34 cases (75.6%) were neonatal onset, the first symptoms of 21 cases (46.7%) were convulsions. 39 cases had been treated with diazoxide, including 12 cases (30.8%) with good efficacy, 16 cases (41%) with poor efficacy and 11 cases with uncertain efficacy. Octreotide was further applied in 18 patients with uncertain or ineffective efficacy after diazoxide treatment, and 13 cases (72.2%) were effective, 3 cases were ineffective, and 2 cases were uncertain. 10 CHI patients who were ineffective to drug treatment or had clearly focal lesions confirmed by 18F-dopa positron emission by computed tomography ( 18F-DOPA PET) scans had undergone surgical treatment, 8 of which underwent partial pancreatectomy and blood glucose returned to normal after the operation; the other 2 cases underwent subtotal pancreatectomy and both had secondary diabetes after operation. Among 45 children with K ATP-HI, 1 case carried both ABCC8 and KCNJ11 mutations, 10 cases carried ABCC8 compound heterozygous mutations, and the remaining 34 cases carried ABCC8/KCNJ11 single genetic mutation. Among them, 21 cases had paternal inheritance, and 3 cases had maternal inheritance, 6 cases were identified with de novo mutations. Conclusions:Diazoxide treatment was ineffective for most K ATP-HI children, but octreotide had a higher effective rate. Partial pancreatectomy for focal type patients had a higher cure rate, and there was a risk of secondary diabetes after subproximal pancreatectomy, so it was very important to clarify the histological type of children before surgery. ABCC8 gene mutations and KCNJ11 gene mutations were the main pathogenic genes of K ATP-HI. Among patients carrying mutations in single ABCC8 or KCNJ11 gene mutation, K ATP-HI inherited by paternity were the majority. Some K ATP-HI children can relieve the hypoglycemia symptoms by themselves.

11.
Chinese Pharmacological Bulletin ; (12): 105-109, 2022.
Article de Chinois | WPRIM | ID: wpr-1014180

RÉSUMÉ

Aim To study the electrophysiological mechanism of dopamine inhibiting insulin secretion hv voltage-dependent potassium ( Kv) channels.Methods Islets and (3 cells were isolated from male SD rats.D,-like receptor agonist ( SKP38393), D2-like receptor agonist (Quinpirole) and antagonist (Epiclopride) were used according to the experiment.Insulin secretion was detected by insulin radioimmunoassay.Whole-cell j J patch-clamp technique was applied to detect Kv channel currents and action potential duration of p cells.Di- BAC4(3) staining was used to observe membrane potential.Results SKF38393 did not affect insulin secretion and the Kv channel currents.Quinpirole signifi cantly inhibited insulin secretion and increased Kv channel currents.Dopamine significantly inhibited insulin secretion, increased Kv channel currents and shortened action potential duration of p cells, which could be reversed by epiclopride.In addition, dopamine de-creased membrane potential of INS-1 cells.Conclusions Dopamine inhibits insulin secretion by acting on D2-like receptors, resulting in actived Kv channels, shortened action potential duration and decreased cell membrane potential.

12.
J. biomed. eng ; Sheng wu yi xue gong cheng xue za zhi;(6): 224-231, 2021.
Article de Chinois | WPRIM | ID: wpr-879269

RÉSUMÉ

As a noninvasive neuromodulation technique, transcranial magnetic stimulation (TMS) is widely used in the clinical treatment of neurological and psychiatric diseases, but the mechanism of its action is still unclear. The purpose of this paper is to investigate the effects of different frequencies of magnetic stimulation (MS) on neuronal excitability and voltage-gated potassium channels in the


Sujet(s)
Animaux , Souris , Potentiels d'action , Phénomènes magnétiques , Troubles mentaux , Neurones , Techniques de patch-clamp , Canaux potassiques voltage-dépendants
13.
Chinese Journal of Anesthesiology ; (12): 1361-1365, 2021.
Article de Chinois | WPRIM | ID: wpr-933256

RÉSUMÉ

Objective:To evaluate the relationship between the euchromatic histone-lysine N-methyltransferase (G9a) and sodium-dependent activation of potassium channel (Slack) in the dorsal root ganglia (DRG) of rats with neuropathic pain (NP).Methods:Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 1 month, weighing 100-120 g, were divided into 4 groups ( n=12 each) by a random number table method: sham operation group (S group), vector plus sham operation group (VS group), vector plus NP group (VN group), and G9a CRISPR/Cas9 knockout plus NP group (GN group). Sham operation was performed at the age of 2 months in group S. In group VS, AAV5 1 μl was microinjected into L 4 and L 5 DRG at the age of 1 month, and sham operation was performed at the age of 2 months.In VN group and GN group, AAV5 and G9a CRISPR/Cas9 knockout plasmid 1 μl were microinjected into L 4 and L 5 DRG at the age of 1 month, and NP model was established by spinal nerve ligation (SNL) at the age of 2 months.Six rats in each group were selected to measure the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) before microinjection (T 0), before SNL (T 1), and at 3, 5 and 7 days after SNL (T 2-4). The animals were sacrificed after the last behavioral testing, the DRGs of lumbar segment (L 4, 5) were removed for determination of the expression of G9a, dimethylation of histone H3 at lysine 9(H3K9me2) and Slack (by Western blot). At 7 days after establishing the model, 6 rats from each group were selected to culture the primary DRG neurons.The frequency and amplitude of Slack current in DRG neurons and miniature excitatory post-synaptic currents (mEPSCs) in the spinal dorsal horn were measured by whole-cell patch-clamp technique. Results:Compared with group S, the TWL was significantly shortened and the MWT was decreased at T 2-4, the expression of G9a and H3K9me2 in the spinal dorsal horn was up-regulated, the expression of Slack was down-regulated, the amplitude and frequency of Slack currents in DRG neurons were decreased, and the frequency of mEPSCs was increased in group VN ( P<0.05), and no significant change was found in the parameters mentioned above in group VS ( P>0.05). Compared with group VN, the TWL was significantly prolonged and the MWT was increased at T 2-4, the expression of G9a and H3K9me2 in the spinal dorsal horn was down-regulated, the expression of Slack was up-regulated, the amplitude and frequency of Slack currents in DRG neurons were increased, and the frequency of mEPSCs was decreased in group GN ( P<0.05). Conclusion:The mechanism of NP is related to up-regulating the expression of G9a in DRG, thus inhibiting the expression and opening of Slack channels in rats.

14.
Article de Chinois | WPRIM | ID: wpr-1016168

RÉSUMÉ

Visceral hypersensitivity is one of the pathogenesis of functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome and functional dyspepsia. In recent years, more and more studies have suggested that the occurrence of gastrointestinal hypersensitivity is related to the changes of neuronal plasticity in the intestinal nervous system or afferent pathway, and potassium channels play a crucial role in controlling neuronal excitability. Lots of studies have shown that decreased expressions or activities of voltage-gated potassium channels, calcium-activated potassium channels, and two-pore domain potassium channels in nociceptors can increase the excitability of neurons, increase visceral pain, and participate in the occurrence of FGIDs. This article reviewed the research progress on relationship between potassium channels and visceral hypersensitivity.

15.
Zhongguo yi xue ke xue yuan xue bao ; Zhongguo yi xue ke xue yuan xue bao;(6): 108-116, 2020.
Article de Chinois | WPRIM | ID: wpr-793055

RÉSUMÉ

G protein-gated inward rectifier potassium(GIRK)channels are widely distributed in the central nervous system and play important roles in maintaining the resting membrane potential of neurons,adjusting neuronal excitability,and regulating the release of neurotransmitter.Studies have shown that addictive behavior is closely related to the expression and activity of the GIRK channels in the brain reward system and the GIRK channels may be a potential target for addiction treatment.This article summarizes the recent research advances in GIRK channels in terms of structure,intracranial tissue distribution,and especially substance addiction.

16.
Article de Chinois | WPRIM | ID: wpr-855929

RÉSUMÉ

Objective To observe the protective effects of fluoxetine on working memory impairment induced by chronic cerebral ischemia and further explore its mechanism in rats. Methods The rat model of chronic cerebral ischemia was made by surgical ligation of the bilateral carotid artery. 44 male Sprague Dawley rats were divided into sham group (n = 10) , ischemic model group (ra = 12), ischemic + fluoxetine group (n = 12) , and sham + fluoxetine group (n = 10). Fluoxetine was administered by gavage after 1 week of ischemic surgery and continued for 4 weeks. The sham group and the ischemic model group were given the same volume of 0. 9% saline. The performance of working memory was tested by a modified Morris water maze experiment that lasted for 4 days. The expression of neuronal nuclei (NeuN) , S-100(3, G protein gated inwardly rectifying K channels 1,2, and 3 ( GirKl , 2 , and 3 ) , and sorting nexin 27 ( SNX27 ) in the prefrontal cortex ( PFC) of rats were tested by Western blot, and compare between groups. Results (1) There was no significant difference in swimming speed among the four groups ( P > 0.05 ). In the training experiment, there was no significant difference among the four groups in the escape latency and the swimming distance ( both P > 0.05 ). In the memory retention test, the escape latency of rats in the ischemic model group was significantly increased on 2nd, 3rd and 4th day compared with the sham group (day2: [48.2 ±6. 3] s vs. [27.4±4.0]s, day 3 :[53.9 ±6.4] s vs. [29.4±6.3]s, day4: [41.4± 4. 9] s vs. [23.8 ±3.7] s; all P 0.05). (3) There was no significant difference in the membrane expression of GirKl protein among the four groups (P > 0. 05). Taking the sham group as a reference and the relative grey value of GirK2 and GirK3 is defined as 1, the relative grey values of GirK2 in the ischemia model group and the ischemia + fluoxetine group were 1. 27 ± 0. 07 and 1. 06 ±0.06, the relative grey values of GirK3 in the ischemia model group and the ischemia + fluoxetine group were 1.23 ±0.08 and 1.00 ±0.06. The membrane expression of GirK2 and GirK3 in the ischemic model group was higher than that in the sham group. The membrane expression of GirK2 and GirK3 in the ischemic + fluoxetine group was down-regulated compared with the ischemic model group ( both P < 0. 05). (4) Taking the sham group as a reference and the relative grey value of SNX27 in the sham group is defined as 1, the relative grey values of SNX27 in the ischemia model group, the ischemia + fluoxetine group, and the sham + fluoxetine group were 0. 78 ± 0.09, 0.97 ± 0.04, and 0. 94 ±0.05, respectively. The expression of SNX27 in the ischemic model group was lower than that in the sham group, and the down-regulation of SNX27 expression in the ischemic model group was reversed after fluoxetine treatment (P<0. 05). Conclusion Fluoxetine can ameliorate working memory impairment of rats induced by chronic cerebral ischemia, which may partly reverse the increase of surface expression of GirK2 and GirK3 in the prefrontal cortex through acting on SNX27.

17.
J. venom. anim. toxins incl. trop. dis ; J. venom. anim. toxins incl. trop. dis;26: e20190043, 2020. tab, graf, ilus
Article de Anglais | LILACS, VETINDEX | ID: biblio-1135134

RÉSUMÉ

The tarantula Chilobrachys jingzhao is one of the largest venomous spiders in China. In previous studies, we purified and characterized at least eight peptides from C. jingzhao venom. In this report, we describe the purification and characterization of Jingzhaotoxin-X (JZTX-X), which selectively blocks Kv4.2 and Kv4.3 potassium channels. Methods: JZTX-X was purified using a combination of cation-exchange HPLC and reverse-phase HPLC. The amino-acid sequence was determined by automated Edman degradation and confirmed by mass spectrometry (MS). Voltage-gated ion channel currents were recorded in HEK293t cells transiently transfected with a variety of ion channel constructs. In addition, the hyperalgesic activity of JZTX-X and the toxin´s effect on motor function were assessed in mice. Results: JZTX-X contained 31 amino acids, with six cysteine residues that formed three disulfide bonds within an inhibitory cysteine knot (ICK) topology. In whole-cell voltage-clamp experiments, JZTX-X inhibited Kv4.2 and Kv4.3 potassium channels in a concentration- and voltage-dependent manner, without affecting other ion channels (Kv1.1, 1.2, 1.3, 2.1, delayed rectifier potassium channels, high- and low-voltage-activated Ca2+ channels, and voltage-gated sodium channels Nav1.5 and 1.7). JZTX-X also shifted the voltage-dependent channel activation to more depolarized potentials, whereas extreme depolarization caused reversible toxin binding to Kv4.2 channels. JZTX-X shifted the Kv4.2 and Kv4.3 activities towards a resting state, since at the resting potential the toxin completely inhibited the channels, even in the absence of an applied physical stimulus. Intrathecal or intraplantar injection of JZTX-X caused a long-lasting decrease in the mechanical nociceptive threshold (hyperalgesia) but had no effect on motor function as assessed in the rotarod test. Conclusions: JZTX-X selectively suppresses Kv4.2 and Kv4.3 potassium channel activity in a concentration- and voltage-dependent manner and causes long-lasting mechanical hyperalgesia.(AU)


Sujet(s)
Animaux , Venins d'araignée , Araignées , Canaux potassiques Shal
18.
Article de Anglais | WPRIM | ID: wpr-765965

RÉSUMÉ

BACKGROUND/AIMS: Interstitial cells play important roles in gastrointestinal (GI) neuro-smooth muscle transmission. The underlying mechanisms of colonic dysmotility have not been well illustrated. We established a partial colon obstruction (PCO) mouse model to investigate the changes of interstitial cells and the correlation with colonic motility. METHODS: Western blot technique was employed to observe the protein expressions of Kit, platelet-derived growth factor receptor-α (Pdgfra), Ca²⁺-activated Cl⁻ (Ano1) channels, and small conductance Ca²⁺- activated K⁺ (SK) channels. Colonic migrating motor complexes (CMMCs) and isometric force measurements were employed in control mice and PCO mice. RESULTS: PCO mice showed distended abdomen and feces excretion was significantly reduced. Anatomically, the colon above the obstructive silicone ring was obviously dilated. Kit and Ano1 proteins in the colonic smooth muscle layer of the PCO colons were significantly decreased, while the expression of Pdgfra and SK3 proteins were significantly increased. The effects of a nitric oxide synthase inhibitor (L-NAME) and an Ano1 channel inhibitor (NPPB) on CMMC and colonic spontaneous contractions were decreased in the proximal and distal colons of PCO mice. The SK agonist, CyPPA and antagonist, apamin in PCO mice showed more effect to the CMMCs and colonic smooth muscle contractions. CONCLUSIONS: Colonic transit disorder may be due to the downregulation of the Kit and Ano1 channels and the upregulation of SK3 channels in platelet-derived growth factor receptor-α positive (PDGFRα⁺) cells. The imbalance between interstitial cells of Cajal-Ano1 and PDGFRα-SK3 distribution might be a potential reason for the colonic dysmotility.


Sujet(s)
Animaux , Souris , Abdomen , Apamine , Technique de Western , Canaux chlorure , Côlon , Régulation négative , Fèces , Cellules interstitielles de Cajal , Muscles lisses , Complexe moteur migrant , Nitric oxide synthase , Facteur de croissance dérivé des plaquettes , Silicium , Silicone , Canaux potassiques calcium-dépendants de petite conductance , Régulation positive
19.
Journal of Chinese Physician ; (12): 1281-1286, 2019.
Article de Chinois | WPRIM | ID: wpr-791134

RÉSUMÉ

Epilepsy is one of the commonest neurological disorder,and genetic factors play a major role in the etiology of epilepsy disorders.In recent years,more and more attention has been paid on the study of potassium channel and epilepsy.The classification of potassium channels is complex,and variants in these genes can lead to a variety of phenotypes from the severest to the mildest,from early infantile epileptic encephalopathy (EIEE) to benign familial neonatal convulsion (BFNC).Moreover,patients with mutations in the same gene may exhibit with distinctive clinical manifestations,the channel dysfunction caused by the variants is correlated with the severity of the disorder.To achieve accurate treatment,the change of channel function is needed to be studied,and more attention should be paid on the development of targeted drugs.

20.
Journal of Chinese Physician ; (12): 1281-1286, 2019.
Article de Chinois | WPRIM | ID: wpr-798084

RÉSUMÉ

Epilepsy is one of the commonest neurological disorder, and genetic factors play a major role in the etiology of epilepsy disorders. In recent years, more and more attention has been paid on the study of potassium channel and epilepsy. The classification of potassium channels is complex, and variants in these genes can lead to a variety of phenotypes from the severest to the mildest, from early infantile epileptic encephalopathy (EIEE) to benign familial neonatal convulsion (BFNC). Moreover, patients with mutations in the same gene may exhibit with distinctive clinical manifestations, the channel dysfunction caused by the variants is correlated with the severity of the disorder. To achieve accurate treatment, the change of channel function is needed to be studied, and more attention should be paid on the development of targeted drugs.

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