Neurotransmission in the carotid body: transmitters and modulators between glomus cells and petrosal ganglion nerve terminals

The carotid body (CB) is the main arterial chemoreceptor. The most accepted model of arterial chemoreception postulates that carotid body glomus (type 1) cells are the primary receptors, which are synaptically connected to the nerve terminals of petrosal ganglion (PG) neurons. In response to natural stimuli, glomus cells are expected to release one (or more) transmitter(s) which, acting on the peripheral nerve terminals of processes from chemosensory petrosal neurons, increases the sensory discharge. Among several molecules present in glomus cells, acetylcholine and adenosine nucleotides and dopamine are considered as excitatory transmitter candidates. In this review, we will examine recent evidence supporting the notion that acetylcholine and adenosine 5'-triphosphate are the main excitatory transmitters in the cat and rat carotid bodies. On the other hand, dopamine may act as a modulator of the chemoreception process in the cat, but as an excitatory transmitter in the rabbit carotid bod

Time structure, temporal correlation and coherence of chemosensory impulses propagated through both carotid nerves in cats

In spontaneously breathing, pentobarbitone anesthetized cats, we recorded simultaneously the impulses in the chemosensory fibers of both carotid (sinus) nerves, to analyze the correlations between the frequencies of chemosensory discharges (f(χ)) and their activation ({df(χ)/dt}(a)) and deactivation ({df(χ)/dt}(d)) rates. We studied the chemosensory responses to brief exposures to hypoxia (100% N2; 5-s and 10-s) and hyperoxia (100% O2; 30-s), and intravenous injections of excitatory (NaCN 0.2-100 μg/kg) and inhibitory (dopamine hydrochloride 0.02-20 μg/kg) chemoreceptor agents. Hypoxia increased f(χ) with a high temporal correlation between frequency levels in both nerves. Prolonging hypoxic stimulation increased {df(χ)/dt}(d), with preservation of {df(χ)/dt}(a). Hyperoxic exposure produced highly correlated decreases in fχ in both nerves, but reduced correlation if df(χ)/dt. Increasing doses of NaCN produced analogous increments in f(χ), df(χ)/dt and their correlations, the {df(χ)/dt

Sodium nitroprusside blocks the cat carotid chemosensory inhibition induced by dopamine, but not that by hyperoxia

We studied the effects of the nitric oxide (NO) synthase inhibitor, Nω- nitro-L-arginine methyl ester (L-NAME), and the NO donor, sodium nitroprusside (SNP) on cat chemosensory responses to intravenous injections of NaCN (0.1-100 μg/kg) and dopamine (0.1-20 μg/kg), and to hyperoxic ventilation (100% O2, 60-120 s). Cats were anesthetized with sodium pentobarbitone, paralyzed and artificially ventilated to prevent secondary ventilatory effects. The frequency of chemosensory discharges (f(x)) was recorded from one sectioned carotid sinus nerve. L-NAME (50 mg/kg i.v.) increased basal f(x) and slightly potentiated the responses to NaCN and dopamine. SNP (1-2 mg/kg i.v.) increased basal f(x), but reduced the NaCN- induced increases of f(x) over baseline and the transient f(x) inhibitions induced by dopamine, but not those produced by hyperoxia. Present results indicate that besides the known inhibitory effect of NO on chemosensory responses to low PO2, NO also blocks the chemosensory respon

ACh and ATP mediate excitatory transmission in cat carotid identified chemoreceptor units in vitro

Several molecules have been proposed as excitatory transmitters between glomus (type 1) cells and nerve terminals of petrosal ganglion (PG) neurons in the carotid body (CB). We tested whether ACh and ATP have a role to play as excitatory transmitters in the cat CB by recording intracellularly from identified PG neurons functionally connected to the CB in vitro. PG neurons projecting to the CB were classified according to their intracellular responses as: (a) neurons with humped action potentials (hAP neurons) responding phasically to long-lasting depolarizing pulses (53/67), and (b) neurons with smooth action potentials (non-hAP neurons) that fire tonically during long-lasting depolarizations (14/67). CB stimulation by stop flow and/or acidosis induced activity in 28 of 39 hAP-type neurons, being classified as chemosensory, but in none of the non-hAP neurons. Hexamethonium (10 μM) and suramin (100 μM) reversibly abolished the increased discharges evoked in chemosensory neurons (8/9) b

NO modulation of carotid body chemoreception in health and disease

Nitric oxide (NO), at physiological concentrations, is a tonic inhibitory modulator of carotid body (CB) chemosensory discharges. NO modulates the chemoreception process by several mechanisms, indirectly by modifying the vascular tone and oxygen delivery, and directly through the modulation of the excitability of glomus cells and petrosal neurons. In addition to the inhibitory effect, at high concentrations NO has a dual dose-dependent effect on CB chemoreception that depends on the PO2 . In hypoxic conditions, NO is primarily an inhibitory modulator of CB chemoreception, while in normoxia NO increases the chemosensory discharges. In this review, we will examine new evidence supporting the idea that NO is involved in the CB chemosensory potentiation induced by congestive heart failure (CHF) and chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea (OSA). Evidence from patients and experimental animal models indicates that CHF and OSA, as well as CIH, potentiate the carotid hypoxic chemoreflexes, contributing to enhance the sympathetic tone. Moreover, animals exposed to CIH or to pacing-induced CHF showed enhanced baseline CB discharges in normoxia and potentiated chemosensory responses to acute hypoxia. Several molecules and pathways are altered in CHF, OSA and CIH, but the available evidence suggests that a reduced NO production in the CB plays an essential role in both diseases, contributing to enhance the CB chemosensory discharges

Fast activity and oscillatory potential of carp retina in the frequency domain

There are two kinds of fast activity in the ERG: fast retinal potentials (FRP), an irregular series of spiky wavelets and oscillatory potentials (OP), a rhythmic sequence of events. Corneal ERG from nine intact young carps, evoked by extended pulses of diffuse white light under mesopic adaptation, displayed two different groups of wavelets related to ON and OFF, respectively. Stimulation and recording conditions were established to permit separate Fourier analysis of both groups of wavelets. Power distributions of normalized ON spectra showed both a wide dispersion and a high inter-subject variability. All normalized OFF spectra showed, instead, components within a narrow band from 52 to 56 Hz, most of them maximum relative power peaks. It is concluded that FRP originating in highly labile sources dominate ON fast activity, while the predominant OFF fast activity are OP originating in a stable discrete source. © 1989

Are there interactions between acetylcholine- and ATP-induced responses at the level of a visceral sensory ganglion?

We investigate possible interactions between acetylcholine (ACh)- and adenosine 5'-triphosphate (ATP)-induced responses of petrosal ganglion, where the perikarya of most sensory neurons of the glossopharyngeal nerve are located. Experiments were performed on petrosal ganglia excised from pentobarbitone-anesthetized cats, desheathed and perfused in vitro. Separate applications of ACh and ATP to the exposed surface of the ganglion induced bursts of antidromic potentials recorded from the carotid (sinus) nerve branch of the glossopharyngeal nerve, which frequencies were dependent on the dose of the applied agonists. The simultaneous application of previously determined ED(50)s of ACh and ATP provoked responses corresponding closely to the simple addition of the responses elicited by the separate application of each agent. Responses usually subsided within 1 min of stimuli application but were followed by periods of refractoriness to subsequent application of the same agent. After determining the timing for recovering from desensitization to the ED50s of ACh and ATP applied separately, ACh was applied while the preparation had been desensitized to ATP and then ATP was applied during desensitization to ACh, but responses obtained were similar to control responses induced by each agent separately. In summary, ACh- and ATP-induced responses of petrosal ganglion neurons are simply additive, followed by a few minute lasting desensitization, but cross-desensitization was not observed. Thus, ACh and ATP seem to operate through independent receptors, activating separate ionic channels, whose coincident currents do not interfere each other

Catecholamine release from isolated sensory neurons of cat petrosal ganglia in tissue culture

The petrosal ganglion (PG) is entirely constituted by the perikarya of primary sensory neurons, part of which innervates the carotid body via the carotid sinus nerve (CSN). Application of acetylcholine (ACh) or nicotine (Nic) as well as adenosine 5′-triphosphate (ATP) to the PG in vitro increases the frequency of CSN discharges, an effect that is modified by the concomitant application of dopamine (DA). Since a population of PG neurons expresses tyrosine hydroxylase, and DA is released from the cat carotid body in response to electrical stimulation of C-fibers in the CSN, it is possible that DA may be released from the perikarya of PG neurons. Therefore, we studied whether ACh or Nic, ATP and high KCl could induce DA release from PG neurons in culture. Petrosal ganglia were excised from pentobarbitone-anesthetized adult cats, dissociated and their neurons maintained in culture for 7-21 days. Catecholamine release was measured by amperometry via carbon-fiber microelectrodes. In respons

Responses to hypoxia of petrosal ganglia in vitro

NaCN is a classical stimulus used to elicit discharges from carotid body chemoreceptors. The effect is assumed to be mediated by glomus (type I) cells, which release an excitatory transmitter for the excitation of carotid nerve endings. Since the sensory perikarya of the glossopharyngeal nerve (from which the carotid nerve branches) are located in the petrosal ganglion, we tested whether application of this drug to the petrosal ganglion superfused in vitro elicits antidromic discharges in the carotid nerve. NaCN did indeed cause an intense and prolonged burst of nerve impulses in the carotid nerve, while provoking a less intense and much briefer burst of discharges in the glossopharyngeal branch. Carotid nerve responses to NaCN were reduced and shortened by prior or following application of dopamine to the ganglion. Sodium azide applied to the petrosal ganglion evoked a less intense and much briefer burst of impulses in the carotid nerve. Ganglionar application of 2,4-dinitrophenol di