[2] P2X receptors are present in a diverse array of organisms including humans, mouse, rat, rabbit, chicken, zebrafish, bullfrog, fluke, and amoeba.

On presynaptic and postsynaptic nerve terminals and glial cells throughout the central, peripheral and autonomic nervous systems, P2X receptors have been shown to modulate synaptic transmission.

[22] The relationship between the structure and function of P2X receptors has been the subject of considerable research using site-directed mutagenesis and chimeric channels, and key protein domains responsible for regulating ATP binding, ion permeation, pore dilation and desensitization have been identified.

[25][26] Once ATP binds to the extracellular loop of the P2X receptor, it evokes a conformational change in the structure of the ion channel that results in the opening of the ion-permeable pore.

[3] Of continuing interest is the fact that some P2X receptors (P2X2, P2X4, human P2X5, and P2X7) exhibit multiple open states in response to ATP, characterized by a time-dependent increase in the permeabilities of large organic ions such as N-methyl-D-glucamine (NMDG+) and nucleotide binding dyes such as propidium iodide (YO-PRO-1).

After complex glycosylation in the Golgi apparatus, they are transported to the plasma membrane, whereby docking is achieved through specific members of the SNARE protein family.

[32] The sensitivity of P2X receptors to ATP is strongly modulated by changes in extracellular pH and by the presence of heavy metals (e.g. zinc and cadmium).

The allosteric modulation of P2X receptors by pH and metals appears to be conferred by the presence of histidine side chains in the extracellular domain.

[33] Ivermectin potentiates ATP-gated currents through P2X4 receptors by increasing the open probability of the channel in the presence of ATP, which it appears to do by interacting with the transmembrane domains from within the lipid bilayer.