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Maitotoxin and P2Z/P2X(7) purinergic receptor stimulation activate a common cytolytic pore

W P Schilling1, T Wasylyna, G R Dubyak

  • 1Rammelkamp Center for Education and Research, Department of Physiology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44109, USA. wschilling@metrohealth.org

The American Journal of Physiology
|October 12, 1999
PubMed

Insights

Maitotoxin (MTX) and P2Z/P2X(7) receptor stimulation both induce cell pores, but MTX activates distinct channels. The study shows MTX and P2Z/P2X(7) receptor stimulation activate indistinguishable cytolytic pores.

Area of Science:

  • Cell Biology
  • Ion Channel Physiology
  • Toxicology

Background:

  • Maitotoxin (MTX) affects cell membrane permeability similarly to P2Z/P2X(7) receptor activation.
  • This suggests MTX may directly activate P2Z/P2X(7) receptors or trigger a common pore formation pathway.

Purpose of the Study:

  • To investigate whether MTX directly activates P2Z/P2X(7) receptors or if both activate a shared cytolytic pore.
  • To differentiate between direct receptor activation and common pore formation by MTX.

Main Methods:

  • Examined MTX effects on THP-1 cells (with/without P2Z/P2X(7) receptor upregulation).
  • Tested MTX on wild-type HEK cells and HEK cells overexpressing P2Z/P2X(7) receptors.
  • Assessed MTX impact on BW5147.3 lymphoma cells, which have P2Z/P2X(7) channels poorly linked to pore formation.
  • Compared MTX- and Bz-ATP-induced pore kinetics, size exclusion, and temperature sensitivity.

Main Results:

  • MTX induced biphasic cytosolic Ca(2+) increases and ethidium uptake in THP-1 cells, comparable in cells with upregulated P2Z/P2X(7) receptors.
  • MTX-induced Ca(2+) influx and ethidium uptake were similar in wild-type and P2Z/P2X(7)-expressing HEK cells.
  • MTX increased Ca(2+) but not ethidium uptake in BW5147.3 cells, indicating distinct channel activation.
  • MTX- and Bz-ATP-induced pores exhibited similar kinetics and size exclusion, and MTX-induced pore formation was temperature-sensitive, like P2Z/P2X(7)-induced pores.

Conclusions:

  • MTX activates ion channels distinct from those activated by P2Z/P2X(7) receptor stimulation.
  • Despite distinct channel activation, MTX and P2Z/P2X(7) receptor stimulation generate indistinguishable cytolytic/oncotic pores.

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