**3. P2X7 receptor associated pore**

Activation of the purinergic P2X7 receptor (P2X7R) is rather unusual among ion channels. Brief agonist stimulation induces a non-selective cation-dependent pore, permitting the permeation of monovalent and divalent cations that leads to plasma membrane depolarization (Virginio et al, 1999b). By contrast, a prolonged and repetitive agonist application (at concentrations greater than 100 µM) promotes increased membrane permeability, allowing cellular uptake of fluorescent dyes such as propidium iodide (MW 639) or lucifer yellow (MW 457).

In the last years, some research groups have provided evidence that pannexin-1 (Panx1) hemichannel might be the protein associated with P2X7 receptor pore formation. However, several cells allow the passage of dyes, despite having the pannexin-1 channel blocked (Faria et al, 2005, 2010; Schachter et al 2008; Yan et al 2008). This opens the possibility that other proteins may participate in the formation of the large channel associated with the P2X7 receptor. As mentioned above, there are other proteins capable of forming large pores in plasma membrane.

In keeping with this idea, Faria and collaborators (2009) showed that calcium ionophores may massively increase the intracellular Ca2+ and induce dye uptake. They observed a pore with biophysical and pharmacological characteristics similar to P2X7 receptor pore (Figure 1). In addition, Schilling and colleagues (1999) observed the Maitotoxin opening, a pore able to uptake fluorescent dyes. This pore was also biophysically similar to the P2X7 receptor pore. Herein, we will address some questions about the possible protein candidate (or candidates) responsible for the P2X7 receptor pore formation described above. Moreover, we will discuss the possible events which might be occurring to regulate the opening of these pores in mammalian cells.
