Perspectives: The Ca2+-dependent K+-channel K Ca3.1 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_Ca3.1, K _Ca2.3). Specifically, K_Ca3.1 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_Ca3.1 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.