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The Mg2+ and Mg2+-Nucleotide-Regulated Channel-Kinase TRPM7

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Transient Receptor Potential (TRP) Channels

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 179))

Abstract

TRPM7 is a member of the melastatin-related subfamily of TRP channels and represents a protein that contains both an ion channel and a kinase domain. The protein is ubiquitously expressed and represents the only ion channel known that is essential for cellular viability. TRPM7 is a divalent cation-selective ion channel that is permeable to Ca2+ and Mg2+, but also conducts essential metals such as Zn2+, Mn2+, and Co2+, as well as nonphysiologic or toxic metals such as Ni2+, Cd2+, Ba2+, and Sr2+. The channel is constitutively open but strongly downregulated by intracellular levels of Mg2+ and MgATP and other Mg-nucleotides. Reducing the cellular levels of these regulators leads to activation of TRPM7-mediated currents that exhibit a characteristic nonlinear current-voltage relationship with pronounced outward rectification due to divalent influx at physiologically negative voltages and monovalent outward fluxes at positive voltages. TRPM7 channel activity is also actively regulated following receptor-mediated changes in cyclic AMP (cAMP) and protein kinase A activity. This regulation as well as that by Mg-nucleotides requires a functional endogenous kinase domain. The function of the kinase domain is not completely understood, but may involve autophosphorylation of TRPM7 as well as phosphorylation of other target proteins such as annexin and myosin IIA heavy chain. Based on these properties, TRPM7 is currently believed to represent a ubiquitous homeostatic mechanism that regulates Ca2+ and Mg2+ fluxes based on the metabolic state of the cell. Physiologically, the channel may serve as a regulated transport mechanism for these ions that could affect cell adhesion, cell growth and proliferation, and even cell death under pathological stress such as anoxia.

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Authors and Affiliations

  1. Laboratory of Cell and Molecular Signaling, Center for Biomedical Research, The Queen’s Medical Center, 1301 Punchbowl Street—UHT 8, Honolulu, HI, 96813, USA

    R. Penner & A. Fleig

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  1. R. Penner
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  2. A. Fleig
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Editor information

Editors and Affiliations

  1. Experimentele und Klinische, Pharmakologie und Toxikologie, Universität des Saarlandes, Gebäude 46, 66421, Homburg, Deutschland

    Veit Flockerzi

  2. Laboratorium voor Fysiologie, Katholieke Universiteit Leuven, Campus Gasthuisberg, Herestraat 49, 3000, Leuven, België

    Bernd Nilius

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© 2007 Springer-Verlag Berlin Heidelberg

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Penner, R., Fleig, A. (2007). The Mg2+ and Mg2+-Nucleotide-Regulated Channel-Kinase TRPM7. In: Flockerzi, V., Nilius, B. (eds) Transient Receptor Potential (TRP) Channels. Handbook of Experimental Pharmacology, vol 179. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-34891-7_19

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