Abstract
Opening of K+ channels in vascular smooth muscle (VSM) cells plays a central role in vasodilation caused by various stimuli. Impairment of K+ channel function in VSM cells has been reported in animal models of diabetes mellitus and hypertension. ATP-sensitive potassium channels (KATP) belong to a distinct group of voltage-independent K+ channels, which link metabolism to membrane excitability. These channels are expressed in various tissues including pancreas, cardiac muscle, VSM and brain. The exact subunit composition differs among the tissues in which KATP channels are expressed. The activation of K ATP channels leads to membrane hyperpolarization, which causes vasodilation and decrease in vascular resistance by closing voltage-dependent Ca2+ channels and decreasing Ca2+ influx, thereby reducing the level of intracellular Ca2+. The KATP channels play an important role not only in coronary blood flow regulation but also in protection of cardiovascular cells from ischemia / reperfusion injury. The ability of KATP channels to produce vasodilation has created much interest in these channels as a potential target for the treatment of disorders, where arterial dilation is a desirable therapeutic goal. This review focuses on the KATP channels expressed in the cardiovascular system and their potential therapeutic considerations. Modification in the activity of these channels could be used in the prevention and treatment of cardiovascular diseases. Furthermore, the cardiovascular effects of anti-diabetic drugs, sulfonylureas are discussed in the light of currently available evidence.
Keywords: ATP-sensitive potassium channels, hyperpolarization, hypoxia, vascular smooth muscle, endothelium, vasodilation, ischemia / reperfusion injury