Adenosine 5'-triphosphate (ATP) was first discovered to be a transmitter at some autonomic neuroeffector junctions (1). Extracellular nucleotides were shown to have actions in several tissues, firstly mast cells, macrophages and platelets. P2X and P2Y receptors were distinguished on the basis of agonist selectivity (2). Cloning of these receptor cDNAs showed an extensive distribution of these proteins and their RNAs: for example, P2X receptors on primary afferent nerves are now known to play roles in taste, sensation from hollow viscera, and inflammatory pain (3,4). P2X receptors are ATP-gated ion channels, which form as trimeric proteins from the same or different subunits (P2X1 – P2X7). They are quite distinct from the tetrameric channels (e.g. glutamate receptors) and pentameric channels (e.g. nicotinic receptor family), but similar in membrane topology to epithelial sodium channels (ENaC) and acid-sensing ion channels (ASIC). Activation of P2X receptors by extracellular ATP signals to the cell by depolarization, calcium entry, and by direct coupling to downstream intracellular effectors. This lecture will review the physiological roles of P2X receptors, and focus on the molecular basis of channel function. This will include the structural basis for binding of ATP, the permeation of ions down the central pore, and the molecular re-arrangements that couple binding to gating (5).

References: 

1. Burnstock G (1972). Pharmacol Rev. 24: 509–581.

2. Burnstock G & Kennedy C (1985). Gen Pharmacol, 16: 433–440

3. North RA (2002). Physiol Rev, 82: 1013–1067.

4. Surprenant A & North RA (2009). Annu Rev Physiol, 71: 333–359.

5. Browne LE, Jiang LH, North RA (2010). Trends Pharmacol Sci, 31: 229–237.