POTASSIUM CHANNEL DIVERSITY IN VASCULAR SMOOTH-MUSCLE CELLS

Several recent observations suggest that the vascular medium is a mosa ic of functionally and morphologically unique cell types. This diversi ty includes differences in cell phenotype and expression of cytoskelet al and contractile proteins as well as heterogeneity of the number and activity of potassium (K+) channel types. K+ channels play a role in the regulation of arterial tone and in the control of cell proliferati on. There is evidence for cell to cell, segment to segment, and vascul ar bed to bed diversity of K+ channels that could explain the varying responses of arterial segments or different arteries to stimuli such a s hypoxia, vasoactive drugs, or arterial wall injury. Pulmonary artery vascular smooth muscle cells contain several types of K+ channels, in cluding calcium sensitive (K-Ca), delayed rectifier (KDR), and ATP gat ed (K-ATP). Hypoxic pulmonary vasoconstriction (HPV) is more prominent in the resistance than in the conduit arteries. HPV is initiated by t he inhibition of a K-DR channel, resulting in membrane depolarization, increase in the intracellular calcium, and contraction. We have shown that some pulmonary artery smooth muscle cells are enriched in K-DR c hannels whereas others have more K-Ca, channels. These cells can be di fferentiated by their morphology (using light microscopy and electron microscopy) and their electrical properties (using patch-clamp techniq ues). Although present throughout the pulmonary artery, K-DR-enriched cells are more prominent in the distal-resistance segments whereas K-C a-enriched cells are more prominent in the proximal-conduit segments. Nitric oxide (NO) causes relaxation in part by activating a K-Ca chann el, causing membrane hyperpolarization and inactivation of the voltage -gated calcium channels. NO is a slightly more potent vasodilator in t he conduit than in the resistance pulmonary artery. In summary, the pu lmonary artery may be thought of as a mosaic of cells that have differ ent proportions of key proteins, such as K+ channel subtypes, which co nfer upon the cell an ability to respond to a stimulus (hypoxia or NO) differently than an adjacent cell exposed to the same stimulus. The p revalence of these cells differs from conduit to resistance arteries. Diversity of cell function may be important in physiology and pathophy siology, allowing responses to vasodilators, vasoconstrictors, and pro liferative stimuli to vary within or between vascular beds.