Emerging challenges of assigning P2X7 receptor function and immunoreactivity in neurons

Currently available antibodies to the P2X7 receptor are unreliable determinants of neuronal P2X7 immunoreactivity, owing to staining of a ‘P2X7-like’ protein that is not eliminated by legitimate P2X7 gene-knockout approaches. Despite this, compelling electrophysiological and pharmacological data strongly support a role for P2X7 receptors in neuronal function and injury. A major priority for the field now is to identify the neuronal ‘P2X7-like’ protein and develop effective antibodies selective for neuronal P2X7 immunoreactivity. Until this occurs, we are dependent on rigorous application of multiple pharmacological criteria for attribution of neuronal function to P2X7 receptors in non-human tissues, including greater activity in response to BzATP than to ATP, sensitivity to blockade by nanomolar concentrations of Brilliant Blue-G, irreversible antagonism by periodate-oxidized ATP, and lack of inhibition by suramin.