The Ca2+-dependent K+-channel KCa3.1 as a therapeutic target in cardiovascular disease

The endothelium is an interesting target to modify cardiovascular disease. In addition to the well-known autacoids such as nitric oxide and prostaglandins, a third endothelial pathway exists which relaxes vascular smooth muscle through hyperpolarization (endothelium-dependent hyperpolarization-type dilation). Herein, calcium-activated potassium channels (K-Ca) are crucial in which two types are expressed in endothelial cells (K(Ca)3.1, K(Ca)2.3). Specifically, K(Ca)3.1 is selectively activated by small molecules that are potentially useful as pharmacological compounds which lead to overall vascular dilation including the coronary bed and a decrease in arterial pressure. Conversely, blockade of this channel reduces atherosclerosis and neointima formation since under these conditions K(Ca)3.1 is up-regulated in phenotypically modulated, proliferative smooth muscle cells and supports migration and proliferation. This review briefly summarizes main experimental findings on this channel.