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Pflügers Archiv

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

The role of TRPM channels in cell death

  • S. McNulty
  • E. Fonfria
Invited Review

Abstract

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.

Keywords

TRPM2 TRPM7 Oxidative stress Ion channel Diabetes Neurodegenerative diseases 

Abbreviations

ADPR

Adenine 5′-diphosphoribose

β-NAD+

β-Nicotinamide-adenine dinucleotide

[Ca2+]i

Intracellular free calcium ion concentration

H2O2

Hydrogen peroxide

PARP

Poly(ADP-ribose) polymerase

PKA

Protein kinase A

ROS

Reactive oxygen species

RNS

Reactive nitrogen species

TNF-α

Tumour necrosis factor-α

TRPM2

Melastatin-like transient receptor potential 2

TRPM2-S

TRPM2 dominant negative splice variant

TRPM7

Melastatin-like transient receptor potential 7

Notes

Acknowledgements

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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