Abstract
Acute oxygen (O(2)) sensing is essential for individuals to survive under hypoxic conditions. The carotid body (CB) is the main peripheral chemoreceptor, which contains excitable and O(2)-sensitive glomus cells with O(2)-regulated ion channels. Upon exposure to acute hypoxia, inhibition of K(+) channels is the signal that triggers cell depolarization, transmitter release and activation of sensory fibers that stimulate the brainstem respiratory center to produce hyperventilation. The molecular mechanisms underlying O(2) sensing by glomus cells have, however, remained elusive. Here we discuss recent data demonstrating that ablation of mitochondrial Ndufs2 gene selectively abolishes sensitivity of glomus cells to hypoxia, maintaining responsiveness to hypercapnia or hypoglycemia. These data suggest that reactive oxygen species and NADH generated in mitochondrial complex I during hypoxia are signaling molecules that modulate membrane K(+) channels. We propose that the structural substrates for acute O(2) sensing in CB glomus cells are "O(2)-sensing microdomains" formed by mitochondria and neighboring K(+) channels in the plasma membrane.