ABSTRACT
Inwardly rectifying Kþ channels passing current more readily in the inward rather than outward direction, have been identified in a wide range of tissues including the central nervous system, the heart, immune cells, skeletal muscle, and various types of smooth muscle (1-3). Both strong (IRK) and weakly rectifying (ATP-sensitive; KATP) K
þ channels belonging to the same superfamily (Kir) have been identified in vascular tissue. The mechanism underlying this unique rectification has been attributed to voltagedependent block by intracellular Mg2þ and polyamines (2,3). These channels are important physiologically because they play a crucial role in setting the resting potential (Em) and controlling membrane excitability. This in turn regulates Ca2þ entry into smooth muscle and endothelial cells and influences the level of vascular tone. Channel activity is also intrinsically linked to cell metabolism, responding to changes in ATP, Kþ, pH, and O2 (1). Whether such mechanisms contribute to the adaptive response in the pulmonary circulation of diverting blood supply away from poorly to well ventilated areas of the lung remains unclear but will be discussed in detail in this chapter. Opposing regulation by vasodilator and vasoconstrictor agents activating protein kinase A (PKA) or protein kinase C (PKC) appears to be a consistent feature of KATP channels (1), although hormone regulation has not been clearly demonstrated for IRK channels, except in
endothelial cells (4). However, increasing evidence suggests that these channels may be important targets for growth factors and for the postnatal maturation of the lung. Significant strides have been made toward the molecular identification of Kir channels, although experiments involving gene ‘‘knockout’’ of putative subunits are extremely limited in vascular muscle, and none look at the expression pattern of these subunits during lung development or in response to hypoxia.
