Julio Alcayaga

Publications (59) View all

• Article: Inhibition of rat carotid body glomus cells TASK-like channels by acute hypoxia is enhanced by chronic intermittent hypoxia.

  Fernando C Ortiz, Rodrigo Del Rio, German Ebensperger, Victor Reyes, Julio Alcayaga, Rodrigo Varas, Rodrigo Iturriaga
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  ABSTRACT: Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, enhances carotid body (CB) chemosensory responses to acute hypoxia. In spite of that, the primary molecular target of CIH in the CB remains unknown. A key step of the hypoxic response in the CB is the chemoreceptor cell depolarization elicited by the inhibition of K(+) channels. Thus, we tested the hypothesis that CIH potentiates the hypoxic-induced depolarization of rat CB chemoreceptor cells by enhancing the inhibition of a background K(+) TASK-like channel. Membrane potential, single channel and macroscopic currents were recorded in the presence of TEA and 4-aminopyridine in CB chemoreceptor cells isolated from adult rats exposed to CIH. The CIH treatment did not modify the resting membrane properties but the hypoxic-evoked depolarization increased by 2-fold. In addition, the hypoxic inhibition of the TASK-like channel current was larger and faster in glomus cells from CIH-treated animals. This novel effect of CIH may contribute to explain the enhancing effect of CIH on CB oxygen chemoreception.
  Respiratory Physiology & Neurobiology 12/2012; · 2.24 Impact Factor
• Article: NO modulation of carotid body chemoreception in health and disease.

  Esteban A Moya, Julio Alcayaga, Rodrigo Iturriaga
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  ABSTRACT: 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 [Formula: see text] . 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.
  Respiratory Physiology & Neurobiology 04/2012; · 2.24 Impact Factor
• Article: Rabbit ventilatory responses to peripheral chemoexcitators: effects of chronic hypoxia.

  Julio Alcayaga, Rodrigo Del Rio, Esteban A Moya, Matías Freire, Rodrigo Iturriaga
  Advances in experimental medicine and biology 01/2012; 758:307-13. · 1.09 Impact Factor
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  Available from: uchile.cl

  Article: Responses induced by acetylcholine and ATP in the rabbit petrosal ganglion.

  Carolina R Soto, Fernando C Ortiz, Romina V Vargas, Jorge Arroyo, Julio Alcayaga
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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. · 2.24 Impact Factor
• Chapter: Evidence for Histamine as a New Modulator of Carotid Body Chemoreception

  R. Del Rio, E.A. Moya, J. Alcayaga, R. Iturriaga
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  ABSTRACT: It has been proposed that histamine is an excitatory transmitter between the glomus cells of the carotid body (CB) and the nerve endings of the petrosal ganglion (PG) neurons. The histamine biosynthetic pathway and the presence of histamine H1, H2 and H3 receptors have been reported in the CB. Thus, histamine meets some of the criteria to be regarded as a transmitter. However, there is no evidence that glomus cells contain histamine, or whether its application produces chemosensory excitation. Therefore, we studied its immunocytochemical localization on cat CB and its effects on chemosensory activity. Using perfused and superfused in vitro CB and PG preparations, we assessed the effects of histamine hydrochloride on chemosensory discharges and of histamine H1, H2 and H3 receptor blockers. We found the presence of histamine immunoreactivity in dense-core vesicles in glomus cells. In an in vitro CB preparation we performed pharmacological experiments to characterize histamine effects. The application of histamine hydrochloride (0.5–1,000μg) to the CB produces a dose-dependent increase in the carotid sinus nerve activity. The H1 receptor blockade with pyrilamine 500nM produces partial decrease of the histamine-induced response, whereas the H2 receptor blockade (ranitidine 100μM) fail to abolish the histamine excitatory effects. Antagonism of the H3 receptor results in an increase in carotid body chemosensory activity. On the other hand, application of histamine to the isolated PG had no effect on the carotid nerve discharge. Our results suggest that histamine is a modulator of the carotid body chemoreception through H1 and H3 receptor activation.
  04/2009: pages 177-184;