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10.1073/pnas.1619835114 http://scihub22266oqcxt.onion/10.1073/pnas.1619835114 C5422773!5422773 !28373535     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28373535 &cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28373535 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Proc+Natl+Acad+Sci+U+S+A 2017 ; 114 (18 ): 4811-4815 Nephropedia Template TP {{tp|p=28373535 |t=2017. Dantrolene requires Mg(2+) to arrest malignant hyperthermia |pdf=|usr=}}{{28373535 }} gab.com Text Dantrolene requires Mg(2+) to arrest malignant hyperthermia JO: Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=28373535 #FOAvip Malignant hyperthermia (MH) is a clinical syndrome of skeletal muscle that presents as a hypermetabolic response to volatile anesthetic gases, where susceptible persons may develop lethally high body temperatures. Genetic predisposition mainly arises from mutations on the skeletal muscle ryanodine receptor (RyR). Dantrolene is administered to alleviate MH symptoms, but its mechanism of action and its influence on the Ca(2+) transients elicited by MH triggers are unknown. Here, we show that Ca(2+) release in the absence of Mg(2+) is unaffected by the presence of dantrolene but that dantrolene becomes increasingly effective as cytoplasmic-free [Mg(2+)] (free [Mg(2+)](cyto)) passes mM levels. Furthermore, we found in human muscle susceptible to MH that dantrolene was ineffective at reducing halothane-induced repetitive Ca(2+) waves in the presence of resting levels of free [Mg(2+)](cyto) (1 mM). However, an increase of free [Mg(2+)](cyto) to 1.5 mM could increase the period between Ca(2+) waves. These results reconcile previous contradictory reports in muscle fibers and isolated RyRs, where Mg(2+) is present or absent, respectively, and define the mechanism of action of dantrolene is to increase the Mg(2+) affinity of the RyR (or "stabilize" the resting state of the channel) and suggest that the accumulation of the metabolite Mg(2+) from MgATP hydrolysis is required to make dantrolene administration effective in arresting an MH episode. Twit Text FOAVip Dantrolene requires Mg(2+) to arrest malignant hyperthermia ????Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=28373535 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28373535 #FOAvip English Wikipedia <ref>{{Cite pmid|28373535 }}</ref> Dantrolene requires Mg(2+) to arrest malignant hyperthermia #MMPMID28373535 Choi RH ; Koenig X ; Launikonis BS Proc Natl Acad Sci U S A 2017[May]; 114 (18 ): 4811-4815 PMID28373535 show ga Malignant hyperthermia (MH) is a clinical syndrome of skeletal muscle that presents as a hypermetabolic response to volatile anesthetic gases, where susceptible persons may develop lethally high body temperatures. Genetic predisposition mainly arises from mutations on the skeletal muscle ryanodine receptor (RyR). Dantrolene is administered to alleviate MH symptoms, but its mechanism of action and its influence on the Ca(2+) transients elicited by MH triggers are unknown. Here, we show that Ca(2+) release in the absence of Mg(2+) is unaffected by the presence of dantrolene but that dantrolene becomes increasingly effective as cytoplasmic-free [Mg(2+)] (free [Mg(2+)](cyto)) passes mM levels. Furthermore, we found in human muscle susceptible to MH that dantrolene was ineffective at reducing halothane-induced repetitive Ca(2+) waves in the presence of resting levels of free [Mg(2+)](cyto) (1 mM). However, an increase of free [Mg(2+)](cyto) to 1.5 mM could increase the period between Ca(2+) waves. These results reconcile previous contradictory reports in muscle fibers and isolated RyRs, where Mg(2+) is present or absent, respectively, and define the mechanism of action of dantrolene is to increase the Mg(2+) affinity of the RyR (or "stabilize" the resting state of the channel) and suggest that the accumulation of the metabolite Mg(2+) from MgATP hydrolysis is required to make dantrolene administration effective in arresting an MH episode. |*Malignant Hyperthermia/drug therapy/metabolism/pathology [MESH] |Adult [MESH] |Animals [MESH] |Calcium Signaling/*drug effects [MESH] |Dantrolene/*pharmacology [MESH] |Female [MESH] |Halothane/pharmacology [MESH] |Humans [MESH] |Magnesium/*pharmacology [MESH] |Male [MESH] |Muscle, Skeletal/*metabolism/pathology [MESH] |Rats [MESH] |Rats, Wistar [MESH]Dantrolene requires Mg(2+) to arrest malignant hyperthermia (epmc).pdf DeepDyve Pubget Overpricing