[Potassium Channels in Blood Vessels: Their Role in Health and Disease]
Overview
General Medicine
Public Health
Affiliations
Endothelial cells and vascular smooth muscle cells express four different classes of potassium ion channels: 1) voltage-gated potassium channels (K(V)); 2) Ca2+-activated potassium channels (KCa), including large - (BK(Ca)), intermediate - (IKCa), and small-conductance (SK(Ca)) Ca2+-activated potassium channels; 3) ATP-sensitive potassium channels (K(ATP)); and 4) inwardly rectifying potassium channels (K(IR)). The activation of potassium channels is the main determinant of the cell membrane potential. Therefore, potassium channels participate in the regulation of vascular tone. Endothelium-dependent vasodilators, i.e. nitric oxide (NO), prostacyclin (PGI2), and endothelium-derived hyperpolarizing factor (EDHF), may activate (open) K+ channels in the cell membrane, which allows K+ efflux out of the cell, causing a decrease in membrane potential and hyperpolarization and, as a consequence, closing voltage-gated calcium channels in the cell membrane and vascular muscle relaxation (vasodilatation). Conversely, inhibition (closing) of vascular K+ channels by vasoconstrictors decreases K+ efflux and opens calcium channels, thereby increasing membrane potential, leading to depolarization and vasoconstriction. Dysfunction of the potassium channels is related to the pathogenesis and/or pathomechanism of some cardiovascular diseases, such as hypertension, atherosclerosis (disorders of all types of potassium channels), diabetes (mainly impairment of K(ATP)), and septic shock (hyperactivity of K(ATP)). On the other hand, abnormal vasoconstriction or vasodilatation is likely to be the consequence of defective potassium channel activity. However, increased or decreased function may also constitute a compensatory mechanism for inappropriate vascular tone. Nowadays modulators of potassium channels are used as therapeutic agents in some health disorders. A multitude of outgoing investigations aims at expanding the novel activators and inhibitors of potassium channels, which may provide a unique therapeutic benefit in vascular therapy.
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