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10.1111/cns.12318 http://scihub22266oqcxt.onion/10.1111/cns.12318 25169754!6495118!25169754     free     free     free Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       CNS+Neurosci+Ther 2015 ; 21 (1): 32-9 Nephropedia Template TP {{tp|p=25169754|t=2015. Local anesthetic lidocaine inhibits TRPM7 current and TRPM7-mediated zinc toxicity |pdf=|usr=}}{{25169754}} gab.com Text Local anesthetic lidocaine inhibits TRPM7 current and TRPM7-mediated zinc toxicity JO: CNS Neurosci Ther http://www.kidney.de/pget.php?&tw=1&pmid=25169754 #FOAvip BACKGROUND: Previous study demonstrated that overstimulation of TRPM7 substantially contributes to zinc-mediated neuronal toxicity. Inhibition of TRPM7 activity and TRPM7-mediated intracellular Zn(2+) accumulation may represent a promising strategy in the treatment of stroke. AIMS: To investigate whether local anesthetics lidocaine could inhibit TRPM7 channel and TRPM7-mediated zinc toxicity. METHODS: Whole-cell patch-clamp technique was used to investigate the effect of local anesthetics on TRPM7 currents in cultured mouse cortical neurons and TRPM7-overexpressed HEK293 cells. Fluorescent Zn(2+) imaging technique was used to study the effect of lidocaine on TRPM7-mediated intracellular Zn(2+) accumulation. TRPM7-mediated zinc toxicity in neurons was used to evaluate the neuroprotective effect of lidocaine. RESULTS: (1) Lidocaine dose dependently inhibits TRPM7-like currents, with an IC50 of 11.55 and 11.06 mM in cultured mouse cortical neurons and TRPM7-overexpressed HEK293 cells, respectively; (2) Lidocaine inhibits TRPM7 currents in a use/frequency-dependent manner; (3) Lidocaine inhibits TRPM7-mediated intracellular Zn(2+) accumulation in both cortical neurons and TRPM7-overexpressed HEK293 cells; (4) TRPM7-mediated Zn(2+) toxicity is ameliorated by lidocaine in cortical neurons; (5) QX-314 has a similar inhibitory effect as lidocaine on TRPM7 currents when applied extracellularly; (6) Procaine also shows potent inhibitory effect on the TRPM7 currents in cortical neurons. CONCLUSION: Our data provide the first evidence that local anesthetic lidocaine inhibits TRPM7 channel and TRPM7-mediated zinc toxicity. Twit Text FOAVip Local anesthetic lidocaine inhibits TRPM7 current and TRPM7-mediated zinc toxicity ????CNS Neurosci Ther http://www.kidney.de/pget.php?&tw=1&pmid=25169754 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25169754 #FOAvip English Wikipedia <ref>{{Cite pmid|25169754}}</ref> Local anesthetic lidocaine inhibits TRPM7 current and TRPM7-mediated zinc toxicity #MMPMID25169754 Leng TD; Lin J; Sun HW; Zeng Z; O'Bryant Z; Inoue K; Xiong ZG CNS Neurosci Ther 2015[Jan]; 21 (1): 32-9 PMID25169754show ga BACKGROUND: Previous study demonstrated that overstimulation of TRPM7 substantially contributes to zinc-mediated neuronal toxicity. Inhibition of TRPM7 activity and TRPM7-mediated intracellular Zn(2+) accumulation may represent a promising strategy in the treatment of stroke. AIMS: To investigate whether local anesthetics lidocaine could inhibit TRPM7 channel and TRPM7-mediated zinc toxicity. METHODS: Whole-cell patch-clamp technique was used to investigate the effect of local anesthetics on TRPM7 currents in cultured mouse cortical neurons and TRPM7-overexpressed HEK293 cells. Fluorescent Zn(2+) imaging technique was used to study the effect of lidocaine on TRPM7-mediated intracellular Zn(2+) accumulation. TRPM7-mediated zinc toxicity in neurons was used to evaluate the neuroprotective effect of lidocaine. RESULTS: (1) Lidocaine dose dependently inhibits TRPM7-like currents, with an IC50 of 11.55 and 11.06 mM in cultured mouse cortical neurons and TRPM7-overexpressed HEK293 cells, respectively; (2) Lidocaine inhibits TRPM7 currents in a use/frequency-dependent manner; (3) Lidocaine inhibits TRPM7-mediated intracellular Zn(2+) accumulation in both cortical neurons and TRPM7-overexpressed HEK293 cells; (4) TRPM7-mediated Zn(2+) toxicity is ameliorated by lidocaine in cortical neurons; (5) QX-314 has a similar inhibitory effect as lidocaine on TRPM7 currents when applied extracellularly; (6) Procaine also shows potent inhibitory effect on the TRPM7 currents in cortical neurons. CONCLUSION: Our data provide the first evidence that local anesthetic lidocaine inhibits TRPM7 channel and TRPM7-mediated zinc toxicity. |Anesthetics, Local/chemistry/pharmacology[MESH] |Cells, Cultured[MESH] |Cerebral Cortex/drug effects/physiology[MESH] |HEK293 Cells[MESH] |Humans[MESH] |Intracellular Space/metabolism[MESH] |Ions/metabolism/toxicity[MESH] |Lidocaine/analogs & derivatives/chemistry/*pharmacology[MESH] |Membrane Potentials/drug effects[MESH] |Neurons/drug effects/physiology[MESH] |Neuroprotective Agents/chemistry/*pharmacology[MESH] |Patch-Clamp Techniques[MESH] |Procaine/chemistry/pharmacology[MESH] |Protein Serine-Threonine Kinases/*antagonists & inhibitors/metabolism[MESH] |TRPM Cation Channels/*antagonists & inhibitors/metabolism[MESH]Local anesthetic lidocaine inhibits TRPM7 current and TRPM7-mediated z(epmc).pdf DeepDyve Pubget Overpricing