Involvement of calcium/calmodulin‐dependent protein kinase II in methamphetamine‐induced neural damage

Methamphetamine (METH), an illicit drug, is widely abused in many parts of the world. Mounting evidence shows that METH exposure contributes to neurotoxicity, particularly for the monoaminergic neurons. However, to date, only a few studies have tried to unravel the mechanisms involved in METH-induced non-monoaminergic neural damage. Therefore, in the present study, we tried to explore the mechanisms for METH-induced neural damage in cortical neurons. Our results showed that METH significantly increased intracellular [Ca2+](i) in Ca2+-containing solution rather than Ca2+-free solution. Moreover, METH also upregulated calmodulin (CaM) expression and activated CaM-dependent protein kinase II (CaMKII). Significantly, METH-induced neural damage can be partially retarded by CaM antagonist W7 as well as CaMKII blocker KN93. In addition, L-type Ca2+ channel was also proved to be involved in METH-induced cell damage, as nifedipine, the L-type Ca2+ channel-specific inhibitor, markedly attenuated METH-induced neural damage. Collectively, our results suggest that Ca2+-CaM-CaMKII is involved in METH-mediated neurotoxicity, and it might suggest a potential target for the development of therapeutic strategies for METH abuse. Copyright (c) 2016 John Wiley & Sons, Ltd. Mounting evidence shows that METH exposure contributes to neurotoxicity, especially for the monoaminergic neurons. However, only a few studies have tried to unravel the mechanisms involved in METH-induced non-monoaminergic neural damage. Therefore, in the present study, we tried to explore the mechanisms for METH-induced neural damage in cortical neurons. Our results showed that METH significantly increased intracellular [Ca2+](i) and up-regulated calmodulin (CaM) expression and activated calmodulin-dependent protein kinase II (CaMK II). Noteworthily, METH-induced neural damage can be partially retarded by CaM antagonist W7, CaMK II blocker KN93 and L-type Ca2+ channel specific inhibitor nifedipine. Collectively, our results suggest that Ca2+-CaM-CaMKII is involved in METH-mediated neurotoxicity, and it might suggest a potential target for the development of therapeutic strategies for METH abuse.