Vascular large conductance calcium-activated potassium channels: Functional role and therapeutic potential

Large-conductance Ca2+-activated K+ channels (BKCa or maxiK channels) are expressed in different cell types. They play an essential role in the regulation of various cell functions. In particular, BKCa channels have been extensively studied in vascular smooth muscle cells, where they contribute to the control of vascular tone. They facilitate the feedback regulation against the rise of intracellular Ca2+, membrane depolarization and vasoconstriction. BKCa channels promote a K+ outward current and lead to membrane hyperpolarization. In endothelial cells expression and function of BKCa channels play an important role in the regulation of the vascular smooth muscle activity. Endothelial BKCa channels modulate the biosyntheses and release of various vasoactive modulators and regulate the membrane potential. Because of their regulatory role in vascular tone, endothelial BKCa channels have been suggested as therapeutic targets for the treatment of cardiovascular diseases. Hypertension, atherosclerosis, and diabetes are associated with altered current amplitude, open probability, and Ca2+-sensing of BKCa channels. The properties of BKCa channels and their role in endothelial and vascular smooth muscle cells would address them as potential therapeutic targets. Further studies are necessary to identify the detailed molecular mechanisms of action and to investigate selective BKCa channels openers as possible therapeutic agents for clinical use.