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 (BKC a ), voltage-dependent K+ channels (KV ), ATP-sensitive K+ channels (KATP ), inward rectifier K+ channels (Kir ), 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.