Channels (Austin, Tex.)最新文献_第4页

Molecular pharmacology of the onco-TRP channel TRPV6. 肿瘤TRP通道TRPV6的分子药理学。

Channels (Austin, Tex.) Pub Date : 2023-12-01 Epub Date: 2023-10-15 DOI: 10.1080/19336950.2023.2266669

Arthur Neuberger, Alexander I Sobolevsky

引用次数: 0

A systemic analysis of monocarboxylate transporters in ovarian cancer and possible therapeutic interventions. 卵巢癌症中单羧酸转运蛋白的系统分析及可能的治疗干预措施。

Channels (Austin, Tex.) Pub Date : 2023-12-01 Epub Date: 2023-11-07 DOI: 10.1080/19336950.2023.2273008

Priti Chatterjee, Debaleena Bhowmik, Sib Sankar Roy

{"title":"A systemic analysis of monocarboxylate transporters in ovarian cancer and possible therapeutic interventions.","authors":"Priti Chatterjee, Debaleena Bhowmik, Sib Sankar Roy","doi":"10.1080/19336950.2023.2273008","DOIUrl":"10.1080/19336950.2023.2273008","url":null,"abstract":"Monocarboxylate transporters (MCTs) play an immense role in metabolically active solid tumors by regulating concentration-dependent transport of different important monocarboxylates including pyruvate and lactate and are encoded by the SLC16A family of genes. Given the vast array of functions, these transporters play in oncogenesis, our objective was to look into the association of MCT1 (SLC16A1), MCT2 (SLC16A7), MCT3 (SLC16A8), and MCT4 (SLC16A3) with Epithelial ovarian cancer (EOC) pathophysiology by exploiting various publicly available databases and web resources. Few of the in silico findings were confirmed via in vitro experiments in EOC cell lines, SKOV3 and OAW-42. MCT1 and MCT4 were found to be upregulated at the mRNA level in OC tissues compared to normal. However, only higher level of MCT4 mRNA was found to be associated with poor patient survival. MCT4 was positively correlated with gene families responsible for invasion, migration, and immune modification, proving it to be one of the most important MCTs for therapeutic intervention. We compared the effects of MCT1/2 blocker SR13800 and a broad-spectrum MCT blocker α-Cyano Hydroxy Cinnamic Acid (α-CHCA) and discovered that α-CHCA has a greater effect on diminishing the invasive behavior of the cancer cells than MCT1/2 blocker SR13800. From our study, MCT4 has emerged as a prospective marker for predicting poor patient outcomes and a potential therapeutic target.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"17 1","pages":"2273008"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10631444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71489617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advances in Ca_V1.1 gating: New insights into permeation and voltage-sensing mechanisms. CaV1.1门控的新进展:渗透和电压传感机制的新见解。

Channels (Austin, Tex.) Pub Date : 2023-12-01 DOI: 10.1080/19336950.2023.2167569

Hugo Bibollet, Audra Kramer, Roger A Bannister, Erick O Hernández-Ochoa

引用次数: 0

Voltage gated sodium and calcium channels: Discovery, structure, function, and Pharmacology. 电压门控钠钙通道:发现、结构、功能和药理学。

Channels (Austin, Tex.) Pub Date : 2023-12-01 Epub Date: 2023-11-20 DOI: 10.1080/19336950.2023.2281714

William A Catterall

{"title":"Voltage gated sodium and calcium channels: Discovery, structure, function, and Pharmacology.","authors":"William A Catterall","doi":"10.1080/19336950.2023.2281714","DOIUrl":"10.1080/19336950.2023.2281714","url":null,"abstract":"Voltage-gated sodium channels initiate action potentials in nerve and muscle, and voltage-gated calcium channels couple depolarization of the plasma membrane to intracellular events such as secretion, contraction, synaptic transmission, and gene expression. In this Review and Perspective article, I summarize early work that led to identification, purification, functional reconstitution, and determination of the amino acid sequence of the protein subunits of sodium and calcium channels and showed that their pore-forming subunits are closely related. Decades of study by antibody mapping, site-directed mutagenesis, and electrophysiological recording led to detailed two-dimensional structure-function maps of the amino acid residues involved in voltage-dependent activation and inactivation, ion permeation and selectivity, and pharmacological modulation. Most recently, high-resolution three-dimensional structure determination by X-ray crystallography and cryogenic electron microscopy has revealed the structural basis for sodium and calcium channel function and pharmacological modulation at the atomic level. These studies now define the chemical basis for electrical signaling and provide templates for future development of new therapeutic agents for a range of neurological and cardiovascular diseases.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"17 1","pages":"2281714"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138178172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural basis of properties, mechanisms, and channelopathy of cyclic nucleotide-gated channels. 环状核苷酸门控通道的性质、机制和通道病的结构基础。

Channels (Austin, Tex.) Pub Date : 2023-12-01 Epub Date: 2023-10-31 DOI: 10.1080/19336950.2023.2273165

Zhengshan Hu, Jian Yang

引用次数: 0

Cycling matters: Sex hormone regulation of vascular potassium channels. 循环问题:血管钾通道的性激素调节。

Channels (Austin, Tex.) Pub Date : 2023-12-01 DOI: 10.1080/19336950.2023.2217637

Samuel N Baldwin, Thomas A Jepps, Iain A Greenwood

{"title":"Cycling matters: Sex hormone regulation of vascular potassium channels.","authors":"Samuel N Baldwin, Thomas A Jepps, Iain A Greenwood","doi":"10.1080/19336950.2023.2217637","DOIUrl":"10.1080/19336950.2023.2217637","url":null,"abstract":"Sex hormones and the reproductive cycle (estrus in rodents and menstrual in humans) have a known impact on arterial function. In spite of this, sex hormones and the estrus/menstrual cycle are often neglected experimental factors in vascular basic preclinical scientific research. Recent research by our own laboratory indicates that cyclical changes in serum concentrations of sex -hormones across the rat estrus cycle, primary estradiol, have significant consequences for the subcellular trafficking and function of KV. Vascular potassium channels, including KV, are essential components of vascular reactivity. Our study represents a small part of a growing field of literature aimed at determining the role of sex hormones in regulating arterial ion channel function. This review covers key findings describing the current understanding of sex hormone regulation of vascular potassium channels, with a focus on KV channels. Further, we highlight areas of research where the estrus cycle should be considered in future studies to determine the consequences of physiological oscillations in concentrations of sex hormones on vascular potassium channel function.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"17 1","pages":"2217637"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10228406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9581141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association of respiratory failure with inhibition of NaV1.6 in the phrenic nerve. 膈神经中NaV1.6抑制与呼吸衰竭的关系。

Channels (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19336950.2022.2122309

Rebecca M Klein, Mark E Layton, Hillary Regan, Christopher P Regan, Yuxing Li, Tracey Filzen, Matt Cato, Michelle K Clements, Jixin Wang, Raul Sanoja, Thomas J Greshock, Anthony J Roecker, Joseph E Pero, Ron Kim, Christopher Burgey, Christopher T John, Ying-Hong Wang, Neetesh Bhandari, Arie Struyk, Richard L Kraus, Darrell A Henze, Andrea K Houghton

{"title":"Association of respiratory failure with inhibition of NaV1.6 in the phrenic nerve.","authors":"Rebecca M Klein, Mark E Layton, Hillary Regan, Christopher P Regan, Yuxing Li, Tracey Filzen, Matt Cato, Michelle K Clements, Jixin Wang, Raul Sanoja, Thomas J Greshock, Anthony J Roecker, Joseph E Pero, Ron Kim, Christopher Burgey, Christopher T John, Ying-Hong Wang, Neetesh Bhandari, Arie Struyk, Richard L Kraus, Darrell A Henze, Andrea K Houghton","doi":"10.1080/19336950.2022.2122309","DOIUrl":"https://doi.org/10.1080/19336950.2022.2122309","url":null,"abstract":"As part of a drug discovery effort to identify potent inhibitors of NaV1.7 for the treatment of pain, we observed that inhibitors produced unexpected cardiovascular and respiratory effects in vivo. Specifically, inhibitors administered to rodents produced changes in cardiovascular parameters and respiratory cessation. We sought to determine the mechanism of the in vivo adverse effects by studying the selectivity of the compounds on NaV1.5, NaV1.4, and NaV1.6 in in vitro and ex vivo assays. Inhibitors lacking sufficient NaV1.7 selectivity over NaV1.6 were associated with respiratory cessation after in vivo administration to rodents. Effects on respiratory rate in rats were consistent with effects in an ex vivo hemisected rat diaphragm model and in vitro NaV1.6 potency. Furthermore, direct blockade of the phrenic nerve signaling was observed at exposures known to cause respiratory cessation in rats. Collectively, these results support a significant role for NaV1.6 in phrenic nerve signaling and respiratory function.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"16 1","pages":"230-243"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9578445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10686089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Small molecule targeting NaV1.7 via inhibition of the CRMP2-Ubc9 interaction reduces pain in chronic constriction injury (CCI) rats. 通过抑制CRMP2-Ubc9相互作用靶向NaV1.7的小分子可减轻慢性收缩损伤(CCI)大鼠的疼痛。

Channels (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19336950.2021.2023383

Jiahe Li, Harrison J Stratton, Sabina A Lorca, Peter M Grace, Rajesh Khanna

{"title":"Small molecule targeting NaV1.7 via inhibition of the CRMP2-Ubc9 interaction reduces pain in chronic constriction injury (CCI) rats.","authors":"Jiahe Li, Harrison J Stratton, Sabina A Lorca, Peter M Grace, Rajesh Khanna","doi":"10.1080/19336950.2021.2023383","DOIUrl":"https://doi.org/10.1080/19336950.2021.2023383","url":null,"abstract":"The voltage-gated sodium channel isoform NaV1.7 is a critical player in the transmission of nociceptive information. This channel has been heavily implicated in human genetic pain disorders and is a validated pain target. However, targeting this channel directly has failed, and an indirect approach - disruption of interactions with accessory protein partners - has emerged as a viable alternative strategy. We recently reported that a small-molecule inhibitor of CRMP2 SUMOylation, compound 194, selectively reduces NaV1.7 currents in DRG neurons across species from mouse to human. This compound also reversed mechanical allodynia in a spared nerve injury and chemotherapy-induced model of neuropathic pain. Here, we show that oral administration of 194 reverses mechanical allodynia in a chronic constriction injury (CCI) model of neuropathic pain. Furthermore, we show that orally administered 194 reverses the increased latency to cross an aversive barrier in a mechanical conflict-avoidance task following CCI. These two findings, in the context of our previous report, support the conclusion that 194 is a robust inhibitor of NaV1.7 function with the ultimate effect of profoundly ameliorating mechanical allodynia associated with nerve injury. The fact that this was observed using both traditional, evoked measures of pain behavior as well as the more recently developed operator-independent mechanical conflict-avoidance assay increases confidence in the efficacy of 194-induced anti-nociception.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8741281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39873967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Cardiogenic shock due to yew poisoning rescued by VA-ECMO: case report and literature review. VA-ECMO抢救红豆杉中毒心源性休克1例并文献复习。

Channels (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19336950.2022.2104886

Nikolaus Schreiber, Martin Manninger, Sascha Pätzold, Alexander C Reisinger, Stefan Hatzl, Gerald Hackl, Christoph Högenauer, Philipp Eller

引用次数: 3

Mechanism of carvedilol induced action potential and calcium alternans. 卡维地洛诱导动作电位和钙离子交换的机制。

Channels (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19336950.2022.2055521

Elizabeth Martinez-Hernandez, Giedrius Kanaporis, Lothar A Blatter

{"title":"Mechanism of carvedilol induced action potential and calcium alternans.","authors":"Elizabeth Martinez-Hernandez, Giedrius Kanaporis, Lothar A Blatter","doi":"10.1080/19336950.2022.2055521","DOIUrl":"https://doi.org/10.1080/19336950.2022.2055521","url":null,"abstract":"Carvedilol is a nonspecific β-blocker clinically used for the treatment of cardiovascular diseases but has also been shown to have profound effects on excitation-contraction coupling and Ca signaling at the cellular level. We investigate the mechanism by which carvedilol facilitates Ca transient (CaT) and action potential duration (APD) alternans in rabbit atrial myocytes. Carvedilol lowered the frequency threshold for pacing-induced CaT alternans and facilitated alternans in a concentration-dependent manner. Carvedilol prolonged the sarcoplasmic reticulum (SR) Ca release refractoriness by significantly increasing the time constant τ of recovery of SR Ca release; however, no changes in L-type calcium current recovery from inactivation or SR Ca load were found after carvedilol treatment. Carvedilol enhanced the degree of APD alternans nearly two-fold. Carvedilol slowed the APD restitution kinetics and steepened the APD restitution curve at the pacing frequency (2 Hz) where alternans were elicited. No effect on the CaT or APD alternans ratios was observed in experiments with a different β-blocker (metoprolol), excluding the possibility that the carvedilol effect on CaT and APD alternans was determined by its β-blocking properties. These data suggest that carvedilol contributes to the generation of CaT and APD alternans in atrial myocytes by modulating the restitution of CaT and APD.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"16 1","pages":"97-112"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9067505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9316270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4