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

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 (BK_{C a} ), voltage-dependent K⁺ channels (K_V ), ATP-sensitive K⁺ channels (K_ATP ), inward rectifier K⁺ channels (K_ir ), and tandem two-pore K⁺ channels (K₂ P). 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.