Hypoxia induces an increase in intracellular magnesium via transient receptor potential melastatin 7 (TRPM7) channels in rat hippocampal neurons in vitro.

Abstract

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.

• Authors: Jing Zhang, Fengbo Zhao, Yin Zhao, Jing Wang, Lei Pei, Ning Sun, Jing Shi
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 286 Issue 23 Pg. 20194-207 (Jun 10 2011) ISSN: 1083-351X [Electronic] United States
• PMID: 21487014 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Sweetening Agents
• TRPM Cation Channels
• Protein Serine-Threonine Kinases
• TRPM7 protein, human
• Trpm7 protein, rat
• Magnesium
• Glucose

Topics

• Animals
• Cell Hypoxia (drug effects, physiology)
• Gene Silencing
• Glucose (pharmacology)
• HEK293 Cells
• Hippocampus (cytology, metabolism)
• Humans
• Ion Transport (drug effects, physiology)
• Magnesium (metabolism)
• Neurons (cytology, metabolism)
• Protein Serine-Threonine Kinases
• Rats
• Sweetening Agents
• TRPM Cation Channels (biosynthesis, genetics)