Studies on Glomus Cell Sensitivity to Hypoxia in Carotid Body Slices

Abstract

Oxygen sensing is a fundamental biological process present in almost all life forms (for reviews see Bunn and Poyton, 1996; López-Barneo et al., 2001). In mammals, the survival in acute hypoxia requires fast respiratory and cardiocirculatory adjustments to ensure sufficient O2 supply to the most critical organs such as the brain or the heart. The main O2 sensor mediating the acute responses to hypoxia is the carotid body (CB), a minute bilateral organ at the bifurcation of the carotid artery innervated by afferent chemosensory fibers. In conditions of hypoxemia, the CBs stimulate the brainstem respiratory centers to evoke hyperventilation. Glomus, or type I, cells are electrically excitable (Duchen et al., 1988, López-Barneo et al., 1988) and constitute the major O₂sensitive elements of the CB (López-Barneo et al., 1988, Delpiano and Hescheler, 1989; Peers 1990; Stea and Nurse, 1991, Buckler, 1997). It is broadly accepted that hypoxia signaling in these cells requires the inhibition of O₂- sensitive potassium channels of the plasma membrane, which leads to depolarization, external Ca²⁺influx, and release of the transmitters that activate the afferent sensory fibers (López- Barneo et al., 1993; Urena et al., 1994; Buckler and Vaughan-Jones, 1994; Carpenter et al., 2000; Pardal et al., 2000). This basic scheme of chemotransduction has also been proposed to operate in other 02-sensitive neurosecretory systems, such as cells in the lung neuroepithelial bodies (Youngson et al., 1993), chromaffin cells of the adrenal medulla (Thompson and Nurse, 1998), or PC-12 cells (Zhu et al., 1996).