Involvement of TRPM7 in cell growth as a spontaneously activated Ca 2+ entry pathway in human retinoblastoma cells

Toyohisa Hanano, Yuji Hara, Juan Shi, Hiromitsu Morita, Chisato Umebayashi, Emiko Mori, Hideki Sumimoto, Yushi Ito, Yasuo Mori, Ryuji Inoue

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175 Citations (Scopus)


We investigated the possible involvement of the melastatin family protein TRPM7 in Ca2+-mediated proliferative control of human retinoblastoma (RB) cells. The growth of RB cell was facilitated by elevating the extracellular Ca2+ concentration with a parallel increase in the magnitude of spontaneous Ca2+ influx. Under nystatin-perforated voltage-clamp, RB cells exhibited an outward-rectifying, spontaneous cation current (I spont) having Ca2+/Mg2+-inhibited but -permeating properties. Various cation channel blockers inhibiting I spont (Gd3+, La3+, LOEg08, 2-APB) suppressed the spontaneous Ca2+ influx and decelerated the growth of RB cells with similar efficacies. Excision of the RB cell membrane (inside-out) into MgATP-free solution induced a 70pS single channel activity, which was effectively inhibited by millimolar concentrations of Mg2+ or MgATP. RT-PCR and immunocytochemical experiments revealed the expression of TRPM7 mRNA and protein in RB cells, and heterologous expression of TRPM7 in HEK293 cells reproduced the key features of Ispont. In contrast, elimination of this protein from RB cells by siRNA silencing markedly reduced Ispont density and the magnitude of spontaneous Ca2+ influx, which was paralleled by decreased TRPM7 immunoreactivity, decelerated cell proliferation, and retarded G1/S cell cycle progression. These results suggest a significant regulatory role of TRPM7 for RB cell proliferation as a spontaneously activated Ca2+ influx pathway.

Original languageEnglish
Pages (from-to)403-419
Number of pages17
JournalJournal of Pharmacological Sciences
Issue number4
Publication statusPublished - Aug 2004

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology


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