Browsing by Author "Alcayaga, Julio"

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    Activation of Intra-nodose Ganglion P2X7 Receptors Elicit Increases in Neuronal Activity
    (2023) Alcayaga, Julio; Vera, Jorge; Reyna-Jeldes, Mauricio; Covarrubias, Alejandra A. A.; Coddou, Claudio; Diaz-Jara, Esteban; Del Rio, Rodrigo; Retamal, Mauricio A. A.
    Vagus nerve innervates several organs including the heart, stomach, and pancreas among others. Somas of sensory neurons that project through the vagal nerve are located in the nodose ganglion. The presence of purinergic receptors has been reported in neurons and satellite glial cells in several sensory ganglia. In the nodose ganglion, calcium depletion-induced increases in neuron activity can be partly reversed by P2X7 blockers applied directly into the ganglion. The later suggest a possible role of P2X7 receptors in the modulation of neuronal activity within this sensory ganglion. We aimed to characterize the response to P2X7 activation in nodose ganglion neurons under physiological conditions. Using an ex vivo preparation for electrophysiological recordings of the neural discharges of nodose ganglion neurons, we found that treatments with ATP induce transient neuronal activity increases. Also, we found a concentration-dependent increase in neural activity in response to Bz-ATP (ED50 = 0.62 mM, a selective P2X7 receptor agonist), with a clear desensitization pattern when applied every similar to 30 s. Electrophysiological recordings from isolated nodose ganglion neurons reveal no differences in the responses to Bz-ATP and ATP. Finally, we showed that the P2X7 receptor was expressed in the rat nodose ganglion, both in neurons and satellite glial cells. Additionally, a P2X7 receptor negative allosteric modulator decreased the duration of Bz-ATP-induced maximal responses without affecting their amplitude. Our results show the presence of functional P2X7 receptors under physiological conditions within the nodose ganglion of the rat, and suggest that ATP modulation of nodose ganglion activity may be in part mediated by the activation of P2X7 receptors.
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    ATP- and ACh-induced responses in isolated cat petrosal ganglion neurons
    (2007) Alcayaga, Carmen; Varas, Rodrigo; Valdes, Viviana; Cerpa, Veronica; Arroyo, Jorge; Iturriaga, Rodrigo; Alcayaga, Julio
    Chemoreceptor (glomus) cells of the carotid body are synaptically connected to the sensory nerve endings of petrosal ganglion (PG) neurons. In response to natural stimuli, the glomus cells release transmitters, which acting on the nerve terminals of petrosal neurons increases the chemosensory afferent discharge. Among several transmitter molecules present in glomus cells, acetylcholine (ACh) and adenosine 5'-triphosphate (ATP) are considered to act as excitatory transmitter in this synapse. To test if ACh and ATP play a role as excitatory transmitters in the cat CB, we recorded the electrophysiological responses from PG neurons cultured in vitro. Under voltage clamp, ATP induces a concentration-dependent inward current that partially desensitizes during 20-30 s application pulses. The ATP-induced current has a threshold near 100 nM and saturates between 20-50 mu M. ACh induces a fast, inactivating inward current, with a threshold between 10-50 mu M, and saturates around 1 mM. A large part of the population of PG neurons (60%) respond to both ATP and ACh. Present results support the hypothesis that ACh and ATP act as excitatory transmitters between cat glomus cells and PG neurons. (c) 2006 Elsevier B.V. All rights reserved.
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    Carbamylated form of human erythropoietin normalizes cardiorespiratory disorders triggered by intermittent hypoxia mimicking sleep apnea syndrome
    (LIPPINCOTT WILLIAMS & WILKINS, 2021) Andrade, David C.; Toledo, Camilo; Diaz, Hugo S.; Pereyra, Katherin, V; Schwarz, Karla G.; Diaz Jara, Esteban; Melipillan, Claudia; Rios Gallardo, Angelica P.; Uribe Ojeda, Atenea; Alcayaga, Julio; Quintanilla, Rodrigo A.; Iturriaga, Rodrigo; Richalet, Jean Paul; Voituron, Nicolas; Del Rio, Rodrigo
    Background and objective: Chronic intermittent hypoxia (CIH), one of the main features of obstructive sleep apnea (OSA), enhances carotid body-mediated chemoreflex and induces hypertension and breathing disorders. The carbamylated form of erythropoietin (cEpo) may have beneficial effects as it retains its antioxidant/anti-inflammatory and neuroprotective profile without increasing red blood cells number. However, no studies have evaluated the potential therapeutic effect of cEpo on CIH-related cardiorespiratory disorders. We aimed to determine whether cEpo normalized the CIH-enhanced carotid body ventilatory chemoreflex, the hypertension and ventilatory disorders in rats. Methods: Male Sprague-Dawley rats (250 g) were exposed to CIH (5% O-2, 12/h, 8 h/day) for 28 days. cEPO (20 mu g/kg, i.p) was administrated from day 21 every other day for one more week. Cardiovascular and respiratory function were assessed in freely moving animals. Results: Twenty-one days of CIH increased carotid body-mediated chemoreflex responses as evidenced by a significant increase in the hypoxic ventilatory response (FiO2 10%) and triggered irregular eupneic breathing, active expiration, and produced hypertension. cEpo treatment significantly reduced the carotid body--chemoreflex responses, normalizes breathing patterns and the hypertension in CIH. In addition, cEpo treatment effectively normalized carotid body chemosensory responses evoked by acute hypoxic stimulation in CIH rats. Conclusion: Present results strongly support beneficial cardiorespiratory therapeutic effects of cEpo during CIH exposure.
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    Carotid Body Inflammation: Role in Hypoxia and in the Anti-inflammatory Reflex
    (AMER PHYSIOLOGICAL SOC, 2022) Iturriaga, Rodrigo; Del Rio, Rodrigo; Alcayaga, Julio
    Emergent evidence indicates that the carotid body (CB) chemoreceptor may sense systemic inflammatory molecules and is an afferent arm of the anti-inflammatory reflex. Moreover, a proinflammatory milieu within the CB is involved in the enhanced CB chemosensory responsiveness to oxygen following sustained and intermittent hypoxia. In this review, we focus on the physiopathological participation of CBs in inflammatory diseases, such as sepsis and intermittent hypoxia.