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10.1089/adt.2018.882 http://scihub22266oqcxt.onion/10.1089/adt.2018.882 30835490!6479253!30835490     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Assay+Drug+Dev+Technol 2019 ; 17 (3): 89-99 Nephropedia Template TP {{tp|p=30835490|t=2019. Electrophysiological and Pharmacological Characterization of Human Inwardly Rectifying K(ir)2 1 Channels on an Automated Patch-Clamp Platform |pdf=|usr=}}{{30835490}} gab.com Text Electrophysiological and Pharmacological Characterization of Human Inwardly Rectifying K(ir)2 1 Channels on an Automated Patch-Clamp Platform JO: Assay Drug Dev Technol http://www.kidney.de/pget.php?&tw=1&pmid=30835490 #FOAvip Inwardly rectifying I(K1) potassium currents of the heart control the resting membrane potential of ventricular cardiomyocytes during diastole and contribute to their repolarization after each action potential. Mutations in the gene encoding K(ir)2.1 channels, which primarily conduct ventricular I(K1), are associated with inheritable forms of arrhythmias and sudden cardiac death. Therefore, potential iatrogenic inhibition of K(ir)2.1-mediated I(K1) currents is a cardiosafety concern during new drug discovery and development. K(ir)2.1 channels are part of the panel of cardiac ion channels currently considered for refined early compound risk assessment within the Comprehensive in vitro Proarrhythmia Assay initiative. In this study, we have validated a cell-based assay allowing functional quantification of K(ir)2.1 inhibitors using whole-cell recordings of Chinese hamster ovary cells stably expressing human K(ir)2.1 channels. We reproduced key electrophysiological and pharmacological features known for native I(K1), including current enhancement by external potassium and voltage- and concentration-dependent blockade by external barium. Furthermore, the K(ir) inhibitors ML133, PA-6, and chloroquine, as well as the multichannel inhibitors chloroethylclonidine, chlorpromazine, SKF-96365, and the class III antiarrhythmic agent terikalant demonstrated slowly developing inhibitory activity in the low micromolar range. The robustness of this assay authorizes medium throughput screening for cardiosafety purposes and could help to enrich the currently limited K(ir)2.1 pharmacology. Twit Text FOAVip Electrophysiological and Pharmacological Characterization of Human Inwardly Rectifying K(ir)2 1 Channels on an Automated Patch-Clamp Platform ????Assay Drug Dev Technol http://www.kidney.de/pget.php?&tw=1&pmid=30835490 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=30835490 #FOAvip English Wikipedia <ref>{{Cite pmid|30835490}}</ref> Electrophysiological and Pharmacological Characterization of Human Inwardly Rectifying K(ir)2 1 Channels on an Automated Patch-Clamp Platform #MMPMID30835490 Sanson C; Schombert B; Filoche-Romme B; Partiseti M; Bohme GA Assay Drug Dev Technol 2019[Apr]; 17 (3): 89-99 PMID30835490show ga Inwardly rectifying I(K1) potassium currents of the heart control the resting membrane potential of ventricular cardiomyocytes during diastole and contribute to their repolarization after each action potential. Mutations in the gene encoding K(ir)2.1 channels, which primarily conduct ventricular I(K1), are associated with inheritable forms of arrhythmias and sudden cardiac death. Therefore, potential iatrogenic inhibition of K(ir)2.1-mediated I(K1) currents is a cardiosafety concern during new drug discovery and development. K(ir)2.1 channels are part of the panel of cardiac ion channels currently considered for refined early compound risk assessment within the Comprehensive in vitro Proarrhythmia Assay initiative. In this study, we have validated a cell-based assay allowing functional quantification of K(ir)2.1 inhibitors using whole-cell recordings of Chinese hamster ovary cells stably expressing human K(ir)2.1 channels. We reproduced key electrophysiological and pharmacological features known for native I(K1), including current enhancement by external potassium and voltage- and concentration-dependent blockade by external barium. Furthermore, the K(ir) inhibitors ML133, PA-6, and chloroquine, as well as the multichannel inhibitors chloroethylclonidine, chlorpromazine, SKF-96365, and the class III antiarrhythmic agent terikalant demonstrated slowly developing inhibitory activity in the low micromolar range. The robustness of this assay authorizes medium throughput screening for cardiosafety purposes and could help to enrich the currently limited K(ir)2.1 pharmacology. |*Automation[MESH] |Animals[MESH] |CHO Cells[MESH] |Chloroquine/chemistry/*pharmacology[MESH] |Cricetulus[MESH] |Dose-Response Relationship, Drug[MESH] |Electrophysiological Phenomena[MESH] |Humans[MESH] |Imidazoles/chemistry/*pharmacology[MESH] |Molecular Structure[MESH] |Pentamidine/analogs & derivatives/chemistry/*pharmacology[MESH] |Phenanthrolines/chemistry/*pharmacology[MESH]Electrophysiological and Pharmacological Characterization of Human Inw(epmc).pdf DeepDyve Pubget Overpricing