Pflügers Archiv

, Volume 451, Issue 1, pp 235–242 | Cite as

The role of TRPM channels in cell death

  • S. McNultyEmail author
  • E. Fonfria
Invited Review


Transient receptor potential (TRP) channels of the melastatin-like family (TRPM) play critical roles in mediating cellular responses to a wide range of physiological stimuli that, under certain situations, can induce cell death. To date, two TRPM family members, TRPM2 and TRPM7, have been implicated directly as central components of cell death pathways. TRPM2, a Ca2+-permeant, non-selective cation channel, senses and responds to oxidative stress levels in the cell. TRPM7 is required for cell viability and has been proposed recently to mediate stress-induced cell death in the central nervous system. We review here the evidence for the involvement of these TRPM channels in cell death processes and discuss the mechanisms by which TRPM channel activation occurs. The ability to attenuate expression levels and functionality of these channels is necessary to understand the involvement of TRPM in cell death and we evaluate current approaches for modulation of TRPM channel function. Finally, we discuss the possibility that TRPM channels may provide therapeutic targets for degenerative diseases involving oxidative stress-related pathologies including diabetes and Alzheimer’s disease.


TRPM2 TRPM7 Oxidative stress Ion channel Diabetes Neurodegenerative diseases 



Adenine 5′-diphosphoribose


β-Nicotinamide-adenine dinucleotide


Intracellular free calcium ion concentration


Hydrogen peroxide


Poly(ADP-ribose) polymerase


Protein kinase A


Reactive oxygen species


Reactive nitrogen species


Tumour necrosis factor-α


Melastatin-like transient receptor potential 2


TRPM2 dominant negative splice variant


Melastatin-like transient receptor potential 7



Dr Elena Fonfria was the recipient of an EU Framework V Postdoctoral Fellowship under the project MCFH-2001-00746. We would like to thank Dr S. D. Skapper and Dr C. Rosin for their assistance with primary oligodendrocyte studies. We would like to thank Dr B. A. Miller and Dr W. Zhang for the supplying and permitting the use of TRPM2-S. In addition we thank Drs I. C. B. Marshall, and R. E. Kelsell for their kind help with development of the manuscript.


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Neurology and GI CEDDGlaxoSmithKline Research and Development LimitedHarlowUK

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