Electrophysiological characterization of nicotinic acetylcholine receptors in cat petrosal ganglion neurons in culture: Effects of cytisine and its bromo derivatives

Laboratorio de Neurobiología, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago, Chile.
Brain Research (Impact Factor: 2.83). 02/2006; 1072(1):72-8. DOI: 10.1016/j.brainres.2005.12.006
Source: PubMed

ABSTRACT Petrosal ganglion neurons are depolarized and fire action potentials in response to acetylcholine and nicotine. However, little is known about the subtype(s) of nicotinic acetylcholine receptors involved, although alpha4 and alpha7 subunits have been identified in petrosal ganglion neurons. Cytisine, an alkaloid unrelated to nicotine, and its bromo derivatives are agonists exhibiting different affinities, potencies and efficacies at nicotinic acetylcholine receptors containing alpha4 or alpha7 subunits. To characterize the receptors involved, we studied the effects of these agonists and the nicotinic acetylcholine receptor antagonists hexamethonium and alpha-bungarotoxin in isolated petrosal ganglion neurons. Petrosal ganglia were excised from anesthetized cats and cultured for up to 16 days. Using patch-clamp technique, we recorded whole-cell currents evoked by 5-10 s applications of acetylcholine, cytisine or its bromo derivatives. Agonists and antagonists were applied by gravity from a pipette near the neuron surface. Neurons responded to acetylcholine, cytisine, 3-bromocytisine and 5-bromocytisine with fast inward currents that desensitized during application of the stimuli and were reversibly blocked by 1 microM hexamethonium or 10 nM alpha-bungarotoxin. The order of potency of the agonists was 3-bromocytisine > acetylcholine approximately = cytisine > 5-bromocytisine, suggesting that homomeric alpha7 neuronal nicotinic receptors predominate in cat petrosal ganglion neurons in culture.

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Available from: Rodrigo Iturriaga, Jul 30, 2015
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    • "Agonist and antagonist sensibility indicate the presence of both α7 and α4β4 (Shirahata et al., 2000; Varas et al., 2006) or α4β2 nAChRs (Shirahata et al., 2000), in concordance with immunohistochemical evidence (Shirahata et al., 1998, 2000). "
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    ABSTRACT: The petrosal ganglion is a peripheral sensory ganglion, composed of pseudomonopolar sensory neurons that innervate the posterior third of the tongue and the carotid sinus and body. According to their electrical properties petrosal ganglion neurons can be ascribed to one of two categories: i) neurons with action potentials presenting an inflection (hump) on its repolarizing phase and ii) neurons with fast and brisk action potentials. Although there is some correlation between the electrophysiological properties and the sensory modality of the neurons in some species, no general pattern can be easily recognized. On the other hand, petrosal neurons projecting to the carotid body are activated by several transmitters, with acetylcholine and ATP being the most conspicuous in most species. Petrosal neurons are completely surrounded by a multi-cellular sheet of glial (satellite) cells that prevents the formation of chemical or electrical synapses between neurons. Thus, petrosal ganglion neurons are regarded as mere wires that communicate the periphery (i.e., carotid body) and the central nervous system. However, it has been shown that in other sensory ganglia satellite glial cells and their neighboring neurons can interact, partly by the release of chemical neuro-glio transmitters. This intercellular communication can potentially modulate the excitatory status of sensory neurons and thus the afferent discharge. In this mini review, we will briefly summarize the general properties of petrosal ganglion neurons and the current knowledge about the glial-neuron communication in sensory neurons and how this phenomenon could be important in the chemical sensory processing generated in the carotid body.
    Frontiers in Physiology 11/2014; 5. DOI:10.3389/fphys.2014.00474 · 3.50 Impact Factor
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    • "However , the responses evoked by ACh in the rabbit presented little or no temporal desensitization, and the duration of the responses were dose-dependent. These differences suggest that the nicotinic receptors expressed by PG neurons (Varas et al., 2006) may differ between species. The application of a muscarinic cholinergic agonist to the rabbit PG in vitro had no effect on the basal ongoing activity, but reduced the responses evoked by further applications of ACh to the ganglion. "
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    ABSTRACT: Acetylcholine and ATP appear to mediate excitatory transmission between receptor (glomus) cells and the petrosal ganglion (PG) neuron terminals in the carotid body. In most species these putative transmitters are excitatory, while inhibitory effects had been reported in the rabbit. We studied the effects of the application of acetylcholine and ATP to the PG on the carotid nerve activity in vitro. Acetylcholine and ATP applied to the PG increased the carotid nerve activity in a dose-dependent manner. Acetylcholine-induced responses were mimicked by nicotine, antagonized by hexamethonium, and enhanced by atropine. Bethanechol had no effect on basal activity, but reduced acetylcholine-induced responses. Suramin antagonized ATP-induced responses, and AMP had little effect on the carotid nerve activity. Our results suggest that rabbit PG neurons projecting through the carotid nerve are endowed with nicotinic acetylcholine and purinergic P2 receptors that increase the carotid nerve activity, while simultaneous activation of muscarinic cholinergic receptors reduce the maximal response evoked by nicotinic cholinergic receptor activation.
    Respiratory Physiology & Neurobiology 05/2010; 172(3):114-21. DOI:10.1016/j.resp.2010.05.003 · 1.97 Impact Factor
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    • "Immunohistochemical studies have shown the presence of nicotinic receptor subunits ␣7 and ␣4 in the nerve endings and in the somata of cat PG neurons (Ishizawa et al., 1996; Shirahata et al., 1998). Recently, we used cytisine (a plant alkaloid unrelated to nicotine) and its bromo derivatives, which act as agonists with different affinities, potencies and efficacies at neuronal nicotinic receptors containing ␣4 or ␣7 subunits, to characterize the receptors involved in the response to ACh in isolated cat PG neurons (Varas et al., 2006). Using patch–clamp technique, we recorded whole-cell currents evoked by the ACh, cytisine or its bromo derivatives. "
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    ABSTRACT: The petrosal ganglion (PG) contains the somata of primary afferent neurons that innervate the chemoreceptor (glomus) cells in the carotid body (CB). The most accepted model of CB chemoreception states that natural stimuli trigger the release of one or more transmitters from glomus cells, which in turn acting on specific post-synaptic receptors increases the rate of discharge in the nerve endings of PG neurons. However, PG neurons that project to the CB represent only small fraction (roughly 20%) of the whole PG and their identification is not simple since their electrophysiological and pharmacological properties are not strikingly different as compared with other PG neurons, which project to the carotid sinus or the tongue. In addition, differences reported on the actions of putative transmitters on PG neurons may reflect true species differences. Nevertheless, some experimental strategies have contributed to identify and characterize the properties of PG neurons that innervate the CB. In this review, we examined the electrophysiological properties and pharmacological responses of PG neurons to putative CB excitatory transmitters, focusing on the methods of study and species differences. The evidences suggest that ACh and ATP play a major role in the fast excitatory transmission between glomus cells and chemosensory nerve endings in the cat, rat and rabbit. However, the role of other putative transmitters such as dopamine, 5-HT and GABA is less clear and depends on the specie studied.
    Respiratory Physiology & Neurobiology 08/2007; 157(1):130-9. DOI:10.1016/j.resp.2006.12.006 · 1.97 Impact Factor
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