Chemoreceptor discharges and cytochrome redox changes of the rat carotid body: Role of heme ligands

In superfused in vitro rat carotid body, we recorded chemoreceptor discharg es and the redox state of cytochromes simultaneously to identify the primar y oxygen-sensing protein controlling transmitter release and electrical act ivity of the carotid sinus nerve. These parameters were tested under the in fluence of heme ligands such as oxygen, cyanide, 4-(2-aminoethyl)-benzenesu lfonyl fluoride, and CO. During stimulation, there was an initial increase in discharge frequency followed by a decline or suppression of activity. Ph otometric changes lagged and were maintained as nerve activity decreased. R educing mitochondrial cytochromes by cyanide or prolonged severe hypoxia, s uppressed the chemoreceptor discharge. 4-(2-aminoethyl)-benzenesulfonyl flu oride, a specific inhibitor of the phagocytic cytochrome b(558), also silen ced the chemoreceptors after an initial excitation. CO increased the chemor eceptor discharge under normoxia, an effect inhibited by light, when the cy tochromes were not reduced, When the discharges were depressed by severe hy poxia, exposure to light excited the chemoreceptors and the cytochromes wer e reduced. The rapidity of the chemosensory responses to light and lack of effect on dopamine release from type I cells led us to hypothesize that car otid body type I cells and the apposed nerve endings use different mechanis ms for oxygen sensing: the nerve endings generate action potentials in asso ciation with membrane heme proteins whereas cytosolic heme proteins signal the redox state, releasing modulators or transmitters from type I cells.