Role and regulation of TRP channels in neutrophil granulocytes

Inka Heiner1, Jörg Eisfeld, Andreas Lückhoff

  • 1Institut für Physiologie, Universitätsklinikum der RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.

Cell Calcium
|May 27, 2003
PubMed

Insights

Transient Receptor Potential Melastatin 2 (TRPM2) channels are functionally expressed in neutrophils, responding to cellular signals like ADP-ribose and NAD. This discovery offers new insights into neutrophil granulocyte responses to chemoattractants.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Neutrophil granulocytes play a critical role in the immune response.
  • Transient Receptor Potential (TRP) channels are involved in various cellular functions, including ion transport.
  • Previous studies indicated the presence of TRP channel mRNA in neutrophils, but functional evidence was limited.

Purpose of the Study:

  • To functionally characterize Transient Receptor Potential (TRP) channels expressed in neutrophil granulocytes.
  • To investigate the role of specific TRP channels, particularly TRPM2 and TRPV6, in neutrophil function.
  • To explore novel mechanisms of cation entry regulation in neutrophils.

Main Methods:

  • Reverse transcription polymerase chain reaction (RT-PCR) to detect TRP channel mRNA.
  • Heterologous overexpression experiments in cell lines.
  • Electrophysiological recordings to analyze cation currents and channel activity.
  • Fura-2 technique for calcium imaging.

Main Results:

  • mRNA for TRPC6, TRPM2, TRPV1, TRPV2, TRPV5, and TRPV6 was detected in neutrophil granulocytes.
  • TRPM2 was identified as the only cation channel with characteristic properties functionally expressed in neutrophils.
  • Neutrophil granulocytes transfected with TRPM2 exhibited non-selective cation currents activated by intracellular ADP-ribose and NAD.
  • TRPV6 is a potential candidate for mediating store-operated calcium entry (SOCE).

Conclusions:

  • TRPM2 channels are functionally expressed in neutrophil granulocytes and are activated by ADP-ribose and NAD, suggesting a role in cellular signaling during oxidative bursts and CD38 activation.
  • This novel TRPM2-mediated cation entry pathway may significantly influence neutrophil responses to chemoattractants.
  • TRPV6 is a likely, though not exclusive, subunit involved in store-operated calcium entry (SOCE) in granulocytes.

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