Research Output

2024 2024 2023 2023 2022 2022 2021 2021 2020 2020 2019 2019 2018 2018 2017 2017 2016 2016 2015 2015 0.0 0.0 0.2 0.2 0.4 0.4 0.6 0.6 0.8 0.8 1.0 1.0 1.2 1.2 1.4 1.4 1.6 1.6 1.8 1.8 2.0 2.0
Now showing 1 - 10 of 12
No Thumbnail Available
Publication

Remembrances of Dr. Michael V.L. Bennett by Iberoamerican Colleagues and Friends

2024 , Verónica Abudara , Ricardo C. Araneda , Luis Barrio , Viviana M. Berthoud , Jorge E. Contreras , Eliseo Eugenín , Juan Lerma , Juan A. Orellana , Nicolás Palacios-Prado , Elia Martha Pérez-Armendariz , RETAMAL LUCERO, MAURICIO ANTONIO , Juan C. Sáez

No Thumbnail Available
Publication

Role of Astroglial Hemichannels and Pannexons in Memory and Neurodegenerative Diseases

2016 , Juan A. Orellana , RETAMAL LUCERO, MAURICIO ANTONIO , Rodrigo Moraga-Amaro , Jimmy Stehberg

No Thumbnail Available
Publication

Neuron-Glia crosstalk in the autonomic nervous system and its possible role in the progression of metabolic syndrome: A new hypothesis

2015 , Rodrigo Del Rio , Rodrigo A. Quintanilla , Juan A. Orellana , RETAMAL LUCERO, MAURICIO ANTONIO

No Thumbnail Available
Publication

SARS-CoV-2 spike protein S1 activates Cx43 hemichannels and disturbs intracellular Ca2+ dynamics

2023 , Juan Prieto-Villalobos , Claudia M. Lucero , Maximiliano Rovegno , Gonzalo I. Gómez , Mauricio A. Retamal , Juan A. Orellana

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the ongoing coronavirus disease 2019 (COVID-19). An aspect of high uncertainty is whether the SARS-CoV-2 per se or the systemic inflammation induced by viral infection directly affects cellular function and survival in different tissues. It has been postulated that tissue dysfunction and damage observed in COVID-19 patients may rely on the direct effects of SARS-CoV-2 viral proteins. Previous evidence indicates that the human immunodeficiency virus and its envelope protein gp120 increase the activity of connexin 43 (Cx43) hemichannels with negative repercussions for cellular function and survival. Here, we evaluated whether the spike protein S1 of SARS-CoV-2 could impact the activity of Cx43 hemichannels. Results We found that spike S1 time and dose-dependently increased the activity of Cx43 hemichannels in HeLa-Cx43 cells, as measured by dye uptake experiments. These responses were potentiated when the angiotensin-converting enzyme 2 (ACE2) was expressed in HeLa-Cx43 cells. Patch clamp experiments revealed that spike S1 increased unitary current events with conductances compatible with Cx43 hemichannels. In addition, Cx43 hemichannel opening evoked by spike S1 triggered the release of ATP and increased the [Ca2+]i dynamics elicited by ATP. Conclusions We hypothesize that Cx43 hemichannels could represent potential pharmacological targets for developing therapies to counteract SARS-CoV-2 infection and their long-term consequences.

No Thumbnail Available
Publication

Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala

2012 , Jimmy Stehberg , Rodrigo Moraga‐Amaro , Christian Salazar , Alvaro Becerra , Cesar Echeverría , Juan A. Orellana , Geert Bultynck , Raf Ponsaerts , Luc Leybaert , Felipe Simon , Juan C. Sáez , Mauricio A. Retamal

No Thumbnail Available
Publication

Acute activation of hemichannels by ethanol leads to Ca2+-dependent gliotransmitter release in astrocytes

2024 , Gonzalo I. Gómez , Claudia García-Rodríguez , Jesús E. Marillán , Sergio A. Vergara , Tanhia F. Alvear , Arantza Farias-Pasten , Juan C. Sáez , RETAMAL LUCERO, MAURICIO ANTONIO , Maximiliano Rovegno , Fernando C. Ortiz , Juan A. Orellana

Multiple studies have demonstrated that acute ethanol consumption alters brain function and cognition. Nevertheless, the mechanisms underlying this phenomenon remain poorly understood. Astrocyte-mediated gliotransmission is crucial for hippocampal plasticity, and recently, the opening of hemichannels has been found to play a relevant role in this process. Hemichannels are plasma membrane channels composed of six connexins or seven pannexins, respectively, that oligomerize around a central pore. They serve as ionic and molecular exchange conduits between the cytoplasm and extracellular milieu, allowing the release of various paracrine substances, such as ATP, D-serine, and glutamate, and the entry of ions and other substances, such as Ca2+ and glucose. The persistent and exacerbated opening of hemichannels has been associated with the pathogenesis and progression of several brain diseases for at least three mechanisms. The uncontrolled activity of these channels could favor the collapse of ionic gradients and osmotic balance, the release of toxic levels of ATP or glutamate, cell swelling and plasma membrane breakdown and intracellular Ca2+ overload. Here, we evaluated whether acute ethanol exposure affects the activity of astrocyte hemichannels and the possible repercussions of this phenomenon on cytoplasmatic Ca2+ signaling and gliotransmitter release. Acute ethanol exposure triggered the rapid activation of connexin43 and pannexin1 hemichannels in astrocytes, as measured by time-lapse recordings of ethidium uptake. This heightened activity derived from a rapid rise in [Ca2+]i linked to extracellular Ca2+ influx and IP3-evoked Ca2+ release from intracellular Ca2+ stores. Relevantly, the acute ethanol-induced activation of hemichannels contributed to a persistent secondary increase in [Ca2+]i. The [Ca2+]i-dependent activation of hemichannels elicited by ethanol caused the increased release of ATP and glutamate in astroglial cultures and brain slices. Our findings offer fresh perspectives on the potential mechanisms behind acute alcohol-induced brain abnormalities and propose targeting connexin43 and pannexin1 hemichannels in astrocytes as a promising avenue to prevent deleterious consequences of alcohol consumption.

No Thumbnail Available
Publication

Synaptic functions of hemichannels: A double-edged sword

2018 , Verónica Abudara , RETAMAL LUCERO, MAURICIO ANTONIO , Rodrigo Del Rio , Juan A. Orellana

No Thumbnail Available
Publication

Interferon-γ and high glucose-induced opening of Cx43 hemichannels causes endothelial cell dysfunction and damage

2020 , Juan C. Sáez , Susana Contreras-Duarte , Valeria C. Labra , Cristian A. Santibañez , Luis A. Mellado , Carla A. Inostroza , Tanhia F. Alvear , RETAMAL LUCERO, MAURICIO ANTONIO , Victoria Velarde , Juan A. Orellana

No Thumbnail Available
Publication

Hypertensive Nephropathy: Unveiling the Possible Involvement of Hemichannels and Pannexons

2022 , Claudia M. Lucero , Juan Prieto-Villalobos , Lucas Marambio-Ruiz , Javiera Balmazabal , Tanhia F. Alvear , Matías Vega , Paola Barra , Mauricio A. Retamal , Juan A. Orellana , Gonzalo I. Gómez

Hypertension is one of the most common risk factors for developing chronic cardiovascular diseases, including hypertensive nephropathy. Within the glomerulus, hypertension causes damage and activation of mesangial cells (MCs), eliciting the production of large amounts of vasoactive and proinflammatory agents. Accordingly, the activation of AT1 receptors by the vasoactive molecule angiotensin II (AngII) contributes to the pathogenesis of renal damage, which is mediated mostly by the dysfunction of intracellular Ca2+ ([Ca2+]i) signaling. Similarly, inflammation entails complex processes, where [Ca2+]i also play crucial roles. Deregulation of this second messenger increases cell damage and promotes fibrosis, reduces renal blood flow, and impairs the glomerular filtration barrier. In vertebrates, [Ca2+]i signaling depends, in part, on the activity of two families of large-pore channels: hemichannels and pannexons. Interestingly, the opening of these channels depends on [Ca2+]i signaling. In this review, we propose that the opening of channels formed by connexins and/or pannexins mediated by AngII induces the ATP release to the extracellular media, with the subsequent activation of purinergic receptors. This process could elicit Ca2+ overload and constitute a feed-forward mechanism, leading to kidney damage.

No Thumbnail Available
Publication

Astroglial gliotransmitters released via Cx43 hemichannels regulate NMDAR‐dependent transmission and short‐term fear memory in the basolateral amygdala

2022 , Sergio Linsambarth , Francisco J. Carvajal , Rodrigo Moraga‐Amaro , Luis Mendez , Giovanni Tamburini , Ivanka Jimenez , Daniel Antonio Verdugo , Gonzalo I. Gómez , Nur Jury , Pablo Martínez , Brigitte Zundert , Lorena Varela‐Nallar , Mauricio A. Retamal , Claire Martin , Guillermo A. Altenberg , Mariana C. Fiori , Waldo Cerpa , Juan A. Orellana , Jimmy Stehberg