The Elusive P2X7 Macropore

Area of Science:

• Cell Biology
• Immunology
• Pharmacology

Background:

• Extracellular ATP acts as a damage-associated molecular pattern (DAMP), activating P2X7 receptors (P2X7Rs).
• P2X7Rs are ion channels involved in NLRP3 inflammasome activation and tumor cell growth.
• Overstimulation of P2X7Rs leads to a nonselective plasma membrane 'macropore' allowing large molecule flux.

Purpose of the Study:

• To investigate the molecular identity and function of the P2X7R-dependent conductance pathway.
• To elucidate the role of P2X7R-mediated plasma membrane permeability in pathophysiological processes.
• To provide a basis for developing novel anti-inflammatory and anticancer therapeutics targeting P2X7R.

Main Methods:

• Analysis of P2X7R channel properties and permeability.
• Investigating the relationship between P2X7R activation and plasma membrane changes.
• Reviewing recent reports on P2X7R solute permeability.

Main Results:

• Recent findings suggest P2X7R permeability to organic solutes is an intrinsic property of the channel.
• The molecular identity of the P2X7R-dependent pore remains unknown.
• P2X7R overstimulation opens a macropore allowing passage of large hydrophilic molecules.

Conclusions:

• Understanding P2X7R-dependent plasma membrane permeability changes is crucial.
• This knowledge can guide the rational development of novel anti-inflammatory and anticancer drugs targeting P2X7R pathways.