Potassium channels in vascular smooth muscle: a pathophysiological and pharmacological perspective

• Published in: Fundamental & clinical pharmacology 2019-10, Vol.33 (5), p.504-523
• Main Authors: Dogan, Muhammed Fatih, Yildiz, Oguzhan, Arslan, Seyfullah Oktay, Ulusoy, Kemal Gokhan
• Format: Article
• Language: English
• Subjects: Animals; Arteriosclerosis; Atherosclerosis; Calcium ions; Cell activation; Cell membranes; Channel gating; Depolarization; Diabetes mellitus; Drug development; Drug Development - methods; Humans; Hypercholesterolemia; Hyperpolarization; Hypertension; Ion channels; Lung diseases; Membrane potential; Muscle, Smooth, Vascular - metabolism; Muscles; Pharmacology; Potassium; Potassium - metabolism; Potassium channels; Potassium channels (inwardly-rectifying); Potassium channels (voltage-gated); Potassium Channels - metabolism; Rectifiers; Smooth muscle; Vascular diseases; vascular smooth muscle cells; Vasoconstriction; Vasodilation
• ISSN: 0767-3981; 1472-8206
• DOI: 10.1111/fcp.12461

Potassium (K+) ion channel activity is an important determinant of vascular tone by regulating cell membrane potential (MP). Activation of K+ channels leads to membrane hyperpolarization and subsequently vasodilatation, while inhibition of the channels causes membrane depolarization and then vasoconstriction. So far five distinct types of K+ channels have been identified in vascular smooth muscle cells (VSMCs): Ca+2‐activated K+ channels (BKCa), voltage‐dependent K+ channels (KV), ATP‐sensitive K+ channels (KATP), inward rectifier K+ channels (Kir), and tandem two‐pore K+ channels (K2P). The activity and expression of vascular K+ channels are changed during major vascular diseases such as hypertension, pulmonary hypertension, hypercholesterolemia, atherosclerosis, and diabetes mellitus. The defective function of K+ channels is commonly associated with impaired vascular responses and is likely to become as a result of changes in K+ channels during vascular diseases. Increased K+ channel function and expression may also help to compensate for increased abnormal vascular tone. There are many pharmacological and genotypic studies which were carried out on the subtypes of K+ channels expressed in variable amounts in different vascular beds. Modulation of K+ channel activity by molecular approaches and selective drug development may be a novel treatment modality for vascular dysfunction in the future. This review presents the basic properties, physiological functions, pathophysiological, and pharmacological roles of the five major classes of K+ channels that have been determined in VSMCs.