Depolarization is a critical event in hypoxia-induced glomus cell secretion.

Abstract

Hypoxia chemotransduction within the carotid body is generally believed to be mediated by the glomus cells. Neurotransmitters (primarily dopamine) are stored within glomus cells in dense-cored vesicles, and catecholamine secretion is enhanced by hypoxia. Glomus cells are apposed to afferent terminals of the sinus nerve, and hypoxia-induced release of catecholamines leads to increased sinus nerve spiking activity. Two theories have evolved in an attempt to elucidate the cellular mechanisms involved in hypoxia-induced glomus cell secretion. In one model, hypoxia inhibits an oxygen-sensitive K+ channel, leading to depolarization, activation of voltage-dependent Ca2+ currents, and enhanced secretion of catecholamine due to increased intracellular calcium (Gonzalez et al, 1994). In support of this model, several investigators have observed an inhibition of glomus cell K+ current by hypoxia during patch-clamp recording of isolated glomus cells, and this inhibition appears to be correlated with an increase in [Ca2+]i and enhanced secretion (Montoro et al, 1996). In contrast, others have observed an increase in [Ca2+]i during hypoxia in the absence of extracellular calcium, implicating a second model, in which hypoxia causes release of calcium from intracellular stores, leading to enhanced secretion (Biscoe et al, 1989a; Biscoe & Duchen, 1990). In this second model, depolarization and calcium influx are not important events in the stimulus cascade. This is supported further by observations that membrane potential may actually hyperpolarize, rather than depolarize, during stimulation (Biscoe & Purves, 1989b).