Kir Channel Molecular Physiology, Pharmacology, and Therapeutic Implications

For the past two decades several scholarly reviews have appeared on the inwardly rectifying potassium (Kir) channels. We would like to highlight two efforts in particular, which have provided comprehensive reviews of the literature up to 2010 (Hibino et al., Physiol Rev 90(1):291-366, 2010; Stanfield et al., Rev Physiol Biochem Pharmacol 145:47-179, 2002). In the past decade, great insights into the 3-D atomic resolution structures of Kir channels have begun to provide the molecular basis for their functional properties. More recently, computational studies are beginning to close the time domain gap between in silico dynamic and patch-clamp functional studies. The pharmacology of these channels has also been expanding and the dynamic structural studies provide hope that we are heading toward successful structure-based drug design for this family of K⁺ channels. In the present review we focus on placing the physiology and pharmacology of this K⁺ channel family in the context of atomic resolution structures and in providing a glimpse of the promising future of therapeutic opportunities.