Glomus cells excitation

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... 

That glomus cells exhibit membrane and cytoplasmic changes in response to hypoxia is very well documented (see Refs. 52-54), but the only way to demonstrate that hypoxia-induced glomus cell excitation initiates the full chemoreceptor process is by recording sensory discharges from the adjacent nerve fibers. 

A decrease below the threshold Pq, normally close to 50 Torr, in glomus cells of the carotid body or in the neonatal ductus arteriosus results in an inhibition of the tonic K current. Such oxygen-regulated inhibition of K+ channels, which may be mediated by mitochondria-derived hydrogen peroxide (Archer et al., 2004), results in an increase in cellular excitability, increased Ca + influx, and a resultant increase in the level of Ca + in the cytosol (reviewed by Lopez-Barneo et al., 1999). 

Excitable Cells Carotid Body Glomus Cell as a Primary Example... 

More recently, successful reinnervation of carotid body glomus cells, changes in the electrical properties, pharmacological sensitivity, and reappearance of hypoxic chemosensitivity in petrosal ganglion cells have been reported when explants of both organs are cultured together (31-35). Petrosal ganghon neurons acutely disconnected from the carotid body and superfused in vitro are not excited by hypoxic hypoxia (36). 

However, some investigators have questioned the role of Kv or maxi-K charmels in the hypoxic excitation of glomus cells. The activation thresholds of these charmels are approximately —30 mV Therefore, most charmels would be closed at the normal resting membrane potential ( —50mV) (31). Hypoxic inhibition of... 

Our data indicate that cholinergic receptors modulate Kv channels. Even though the data do not fully provide the underlying mechanisms of this interaction, they have prompted a modification of our view as to how glomus cells are excited. Neurotransmitters appear to contribute to the excitabdity of glomus cells not only by their immediate and direct action on their receptors, but also by their modulating effects on ion channel activities. 

Figure 4 In situ recording of neural trafSc in the whole carotid sinus nerve. Cat carotid body is responding to a perfusion of hypoxic Krebs Ringer bicarbonate solution without (open bars) and with (hatched bars) 4 pM AFDX 116, an M2 receptor inhibitor (mean SEM). This neural response could be due to an increase in ACh release because glomus cell M2-inhibiting autoreceptors are inhibited, releasing a greater amount of ACh. Or the postsynaptic M2 receptors (responsible for the slow inhibitory postsynaptic potential) are inhibited, making the postsynaptic sensory afferent neuron more excitable, or both processes.

In conclusion, the distribution of NOS immunoreactivity and the pharmacological and physiological evidence analyzed and discussed here support the proposal that CB endogenous NO exerts a tonic inhibitory effect on CB chemoreception. Clearly, NO in low concentration is a broad inhibitory modulator of the chemoreception process in the CB. NO may modulate chemoreception by regulating the CB vascular tone, the oxygen delivery to the chemoreceptor cells, and the excitability of glomus cells and petrosal sensory neurons. 

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