Targets in Ischemia and Heart Failure?

Purinergic1 receptors were initially conceived to describe the likely existence of membrane receptors responding to adenosine triphosphate (ATP) (P2 receptors) or its breakdown product adenosine (P1 receptors) in causing nonadrenergic, noncholinergic relaxation of gut smooth muscle.1 Cloning of these receptors has yielded insights into their properties and signaling mechanisms, allowing classification into subfamilies of metabotropic (P2Y and P1) and ionotropic (P2X) receptors based on structure.2 These receptors are now associated with a number of important roles in normal and pathophysiology.3 Adenosine has been used extensively as a vasodilator and an antiarrhythmic, and efforts to target each adenosine receptor subtype as novel therapies are ongoing.4 In this Perspective, we will focus our attention on P2 receptors in the heart (see Figure 1 and the Table for basic characteristics and known cardiac distribution) and more specifically on novel aspects of the P2X4 receptor.