Thomas GRUTTER

PORE DILATION OF P2X RECEPTORS: CONTROVERSY IN THE HOLE

Thomas GRUTTER
Laboratoire de Conception et Application de Molécules Bioactives. Strasbourg

The permeability of large cations through the P2X pore has remained arguably the most controversial and complicated topic in P2X-related research, with the emergence of conflicting studies on the existence, mechanism and physiological relevance of a so-called “dilated” state. Due to the important role of several “dilating” P2X subtypes in numerous diseases, a clear and detailed understanding of this phenomenon represents a research priority. Recent advances, however, have challenged the existence of a progressive, ATP-induced pore dilation, by demonstrating that this phenomenon is an artefact of the method employed. In this talk, I will briefly present the history of this controversial and enigmatic dilated state, from its initial discovery to its recent reconsideration. I will also show how modern chemical optogenetics combined to single-channel recordings have provided new insights into the permeation of large cations. Finally, the physiological relevance of such a large cation-permeable pore will also be discussed.