Cardiac and renal inward rectifier potassium channel pharmacology: emerging tools for integrative physiology and therapeutics

• Some Kir channels are putative drug targets, but their pharmacology is limited.
• Newly discovered inhibitors or activators of Kir2.x, 4.1, and 7.1 are discussed.
• Mechanisms of action involve pore-lining residues that control rectification.
• This work is a critical first step toward developing more specific modulators.

Inward rectifier potassium (Kir) channels play fundamental roles in cardiac and renal function and may represent unexploited drug targets for cardiovascular diseases. However, the limited pharmacology of Kir channels has slowed progress toward exploring their integrative physiology and therapeutic potential. Here, we review recent progress toward developing the small-molecule pharmacology for Kir2.x, Kir4.1, and Kir7.1 and discuss common mechanistic themes that may help guide future Kir channel-directed drug discovery efforts.