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Hypoxia induces an increase in intracellular magnesium via transient receptor
potential melastatin 7 (TRPM7) channels in rat hippocampal neurons in vitro
#MMPMID21487014
Zhang J
; Zhao F
; Zhao Y
; Wang J
; Pei L
; Sun N
; Shi J
J Biol Chem
2011[Jun]; 286
(23
): 20194-207
PMID21487014
show ga
TRPM7, a divalent cation channel, plays an important role in neurons damaged from
cerebral ischemia due to permitting intracellular calcium overload. This study
aimed to explore whether magnesium was transported via a TRPM7 channel into the
intracellular space of rat hippocampal neurons after 1 h of oxygen-glucose
deprivation (OGD) and acute chemical ischemia (CI) by using methods of the Mg(2+)
fluorescent probe Mag-Fura-2 to detect intracellular magnesium concentration
([Mg(2+)](i)) and flame atomic absorption spectrometry to measure extracellular
magnesium concentration ([Mg(2+)](o)). The results showed that the neuronal
[Mg(2+)](i) was 1.51-fold higher after 1 h of OGD at a basal level, and the
increase of neuronal [Mg(2+)](i) reached a peak after 1 h of OGD and was kept for
60 min with re-oxygenation. Meanwhile, the [Mg(2+)](o) decreased after 1 h of OGD
and recovered to the pre-ischemic level within 15 min after re-oxygenation. In
the case of CI, the [Mg(2+)](i) peak immediately appeared in hippocampal neurons.
This increase of [Mg(2+)](i) declined by removing extracellular magnesium in OGD
or CI. Furthermore, by using Gd(3+) or 2-aminoethoxydiphenyl borate to inhibit
TRPM7 channels, the [Mg(2+)](i) increase, which was induced by OGD or CI, was
attenuated without altering the basal level of [Mg(2+)](i). By silencing TRPM7
with shRNA in hippocampal neurons, it was found that not only was the increase of
[Mg(2+)](i) induced by OGD or CI but also the basal levels of [Mg(2+)](i) were
attenuated. In contrast, overexpression of TRPM7 in HEK293 cells exaggerated both
the basal levels and increased [Mg(2+)](i) after 1 h of OGD/CI. These results
suggest that anoxia induced the increase of [Mg(2+)](i) via TRPM7 channels in rat
hippocampal neurons.
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