Glomus cells release from

Using the same coculture techniques, glomus cells with petrosal ganglion cells (PGN) and recording from the PGN neurons, it was shown that PGN cells and their terminals responded to hypoxia and CO2/PH and not the PGN cells alone (Zhong et al., 1997 Prasad et al., 2001 Zhang and Nurse, 2004). This means that neurotransmitters released from the glomus cells excited the PGN cells. These transmitters consisted of ATP and ACh. Similar results were obtained by Varas et al. (2003). Recorded intracellularly from identified PGN functionally connected with the carotid body (CB) in vitro, and which responded to CB stimulation by stop... 

Carpenter E, Hatton CJ, Peers C. Effects of hypoxia and dithionite on catecholamine release from isolated type 1 cells of the rat carotid body. J Physiol 2000 523 719-729. Pardal R, Ludewig U, Garcia-Hirschfeld 1, Lopez-Bameo J. Secretory responses of intact glomus cells in thin shces of rat carotid body to hypoxia and tetraethylammonium. Proc Natl Acad Sci USA 2000 97 2361-2366. 

Figure 1 Schematic diagram illustrating the basic features of chemotransduction from glomus cells to carotid nerve terminals (NT). The glomus cell is packed with dark-core vesicles and contains a plethora of chemical agents (list on the left). Natural stimulation (list at the bottom) releases these agents toward the endings of the carotid nerve (NT). The chemicals cross the synaptic cleft between glomus cells and nerve endings (horizontal open arrows).

The release of neurotransmitters from the glomus cell is assumed to be regulated by... 

Urena J, Femandez-Chacon R, Benot AR, Alvarez de Toledo GA, Lopez-Bameo J. H3 poxia induces voltage-dependent Ca entry and quantal dopamine secretion in carotid hody glomus cells. Proc Natl Acad Sci USA 1994 91(21) 10208-10211. DormeUy DF. Electrochemical detection of catecholamine release from rat carotid body in vitro. JAppl Physiol 1993 74(5) 2330-2337. 

Stimulate and DA can inhibit cat carotid body neural output. Second, nicotinic, muscarinic, and dopaminergic receptors act in the cat carotid body as they do elsewhere. Thus, exocytotically released ACh and DA should stimulate and inhibit, respectively, postsynaptic neural traffic in the carotid sinus nerve. PresynapticaUy (i.e., on the glomus cells) the presence of the receptors would suggest that—as in other species— they can regulate by positive/negative feedback their own release from the glomus cells and, perhaps, the release of other neurotransmitters. 

Figure 3 Effect of an M2 receptor antagonist (4 iM gaHamine) on the release of acetylcholine from paired cat carotid bodies. Acetylcholine (ACh) released from two carotid bodies (average of two runs) was incubated in Krebs Ringer bicarbonate solution at 37°C for 15 min under normoxic conditions (N solution bubbled with 21%02/5%C02) and then for 15 min tmder hypoxic conditions (H solution bubbled with 4%02/5%C02). Gallamine appears to increase the release of ACh during normoxia and particularly during hypoxia. This pair of carotid bodies released only about 25% of the usual amount released. Presumably the ACh released by the carotid bodies acts on glomus cell autoreceptors to attenuate the further release of ACh. But the block by gallamine inhibits the inhibiting receptor more ACh is released.

Several studies have demonstrated that hypoxia releases DA from cat, rabbit, and rat carotid bodies (1,11,18,19,54,59,87). Recent studies using chronoampero-metry in carotid body slices have provided evidence that much of the DA released during hypoxia comes from glomus cells (59). DA release by hypoxia is dependent and involves at least voltage-gated L-type Ca channels (54). Acidosis (pH = 7.2-6.6) as well as high CO2 (20% CO2, pH 7.4) also stimulates DA release from the rabbit carotid body in a Ca " -dependent manner (80). Although type I cells express NE, hypoxia preferentially releases DA more than NE (20,87). 

It is striking that in aU of these O2-sensitive tissues, the effectors appear to be K+ channels (Fig. 2). Isolated PASMCs, ADMCs (or the pheochromocytoma cells, PC 12, used as models for ADMCs), and cells from the CB and NEB respond to hypoxia with a decrease in the outward K+ current (Fig. 2). This results in depolarization of the plasmalemmal membrane, increased opening of voltage-gated Ca + channels, influx of Ca +, and an increase in [Ca +] . In the case of PASMC, this results in the activation of actin-myosin and contraction. In CB glomus cells, it results in release of dopamine from vesicles and increased neural transmission to the brainstem via the IX cranial nerve. Similarly, in ADM and NEB cells K+ current inhibition, membrane depolarization, and increases in [Ca +] cause the release of... 

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