P2X Purinoreceptor - Activation and Channel Opening

Activation and Channel Opening

Three ATP molecules are thought to be required to activate a P2X receptor, suggesting that ATP needs to bind to each of the three subunits in order to open the channel pore, though recent evidence suggests that ATP binds at the three subunit interfaces. 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. The most commonly accepted theory of channel opening involves the rotation and separation of the second transmembrane domain (TM) helices, allowing cations such as Na+ and Ca2+ to access the ion-conducting pore through three lateral fenestrations above the TM domains. The entry of cations leads to the depolarization of the cell membrane and the activation of various Ca2+-sensitive intracellular processes. The channel opening time is dependent upon the subunit makeup of the receptor. For example, P2X₁ and P2X₃ receptors desensitize rapidly (a few hundred milliseconds) in the continued presence of ATP, whereas the P2X₂ receptor channel remains open for as long as ATP is bound to it.