Pflügers Archiv

, Volume 451, Issue 1, pp 235–242

The role of TRPM channels in cell death

Authors

    • Neurology and GI CEDDGlaxoSmithKline Research and Development Limited
  • E. Fonfria
    • Neurology and GI CEDDGlaxoSmithKline Research and Development Limited
Invited Review

DOI: 10.1007/s00424-005-1440-4

Cite this article as:
McNulty, S. & Fonfria, E. Pflugers Arch - Eur J Physiol (2005) 451: 235. doi:10.1007/s00424-005-1440-4

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

TRPM2TRPM7Oxidative stressIon channelDiabetesNeurodegenerative 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

Copyright information

© Springer-Verlag 2005