Open AccessLocal Anesthetic Lidocaine Inhibits TRPM 7 Current and TRPM 7‐Mediated Zinc Toxicity
Author(s) -
Leng TianDong,
Lin Jun,
Sun HuaWei,
Zeng Zhao,
O'Bryant Zaven,
Inoue Koichi,
Xiong ZhiGang
Publication year - 2015
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12318
Subject(s) - trpm7 , patch clamp , pharmacology , lidocaine , microbiology and biotechnology , intracellular , toxicity , medicine , transient receptor potential channel , chemistry , electrophysiology , receptor , anesthesia , biology
Summary Background Previous study demonstrated that overstimulation of TRPM 7 substantially contributes to zinc‐mediated neuronal toxicity. Inhibition of TRPM 7 activity and TRPM 7‐mediated intracellular Zn 2+ accumulation may represent a promising strategy in the treatment of stroke. Aims To investigate whether local anesthetics lidocaine could inhibit TRPM 7 channel and TRPM 7‐mediated zinc toxicity. Methods Whole‐cell patch‐clamp technique was used to investigate the effect of local anesthetics on TRPM 7 currents in cultured mouse cortical neurons and TRPM 7‐overexpressed HEK 293 cells. Fluorescent Zn 2+ imaging technique was used to study the effect of lidocaine on TRPM 7‐mediated intracellular Zn 2+ accumulation. TRPM 7‐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 IC 50 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 TRPM 7 channel and TRPM 7‐mediated zinc toxicity.