Neural depolarization triggers Mg2+ influx in rat hippocampal neurons

R. Yamanaka, Y. Shindo, T. Karube, K. Hotta, Koji Suzuki, K. Oka

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


Homeostasis of magnesium ion (Mg2+) plays key roles in healthy neuronal functions, and deficiency of Mg2+ is involved in various neuronal diseases. In neurons, we have reported that excitotoxicity induced by excitatory neurotransmitter glutamate increases intracellular Mg2+ concentration ([Mg2+]i). However, it has not been revealed whether neuronal activity under physiological condition modulates [Mg2+]i. The aim of this study is to explore the direct relationship between neural activity and [Mg2+]i dynamics. In rat primary-dissociated hippocampal neurons, the [Mg2+]i and [Ca2+]i dynamics were simultaneously visualized with a highly selective fluorescent Mg2+ probe, KMG-104, and a fluorescent Ca2+ probe, Fura Red, respectively. [Mg2+]i increase concomitant with neural activity by direct current stimulation was observed in neurons plated on an indium-tin oxide (ITO) glass electrode, which enables fluorescent imaging during neural stimulation. The neural activity-dependent [Mg2+]i increase was also detected in neurons whose excitability was enhanced by the treatment of a voltage-gated K+ channel blocker, tetraethylammonium (TEA) at the timings of spontaneous Ca2+ increase. Furthermore, the [Mg2+]i increase was abolished in Mg2+-free extracellular medium, indicating [Mg2+]i increase is due to Mg2+ influx induced by neural activity. The direct neuronal depolarization by veratridine, a Na+ channel opener, induced [Mg2+]i increase, and this [Mg2+]i increase was suppressed by the pretreatment of a non-specific Mg2+ channel inhibitor, 2-aminoethoxydiphenyl borate (2-APB). Overall, activity-dependent [Mg2+]i increase results from Mg2+ influx through 2-APB-sensitive channels in rat hippocampal neurons.

Original languageEnglish
Pages (from-to)731-741
Number of pages11
Publication statusPublished - 2015 Dec 3


  • Depolarization
  • Fluorescent imaging
  • Hippocampal neuron
  • ITO electrode
  • KMG-104
  • Mg

ASJC Scopus subject areas

  • General Neuroscience


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