Control of astrocytic Ca<SUP>2+</SUP> signaling by nitric oxide-dependent S-nitrosylation of Ca<SUP>2+</SUP> homeostasis modulator 1 channels

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dc.contributor.authorPuebla, Mariela
dc.contributor.authorMunoz, Manuel F.
dc.contributor.authorLillo, Mauricio A.
dc.contributor.authorContreras, Jorge E.
dc.contributor.authorFigueroa, Xavier F.
dc.date.accessioned2025-01-20T17:05:29Z
dc.date.available2025-01-20T17:05:29Z
dc.date.issued2024
dc.description.abstractBackground Astrocytes Ca2+ signaling play a central role in the modulation of neuronal function. Activation of metabotropic glutamate receptors (mGluR) by glutamate released during an increase in synaptic activity triggers coordinated Ca2+ signals in astrocytes. Importantly, astrocytes express the Ca2+-dependent nitric oxide (NO)-synthetizing enzymes eNOS and nNOS, which might contribute to the Ca2+ signals by triggering Ca2+ influx or ATP release through the activation of connexin 43 (Cx43) hemichannels, pannexin-1 (Panx-1) channels or Ca2+ homeostasis modulator 1 (CALHM1) channels. Hence, we aim to evaluate the participation of NO in the astrocytic Ca2+ signaling initiated by stimulation of mGluR in primary cultures of astrocytes from rat brain cortex. Results Astrocytes were stimulated with glutamate or t-ACPD and NO-dependent changes in [Ca2+](i) and ATP release were evaluated. In addition, the activity of Cx43 hemichannels, Panx-1 channels and CALHM1 channels was also analyzed. The expression of Cx43, Panx-1 and CALHM1 in astrocytes was confirmed by immunofluorescence analysis and both glutamate and t-ACPD induced NO-mediated activation of CALHM1 channels via direct S-nitrosylation, which was further confirmed by assessing CALHM1-mediated current using the two-electrode voltage clamp technique in Xenopus oocytes. Pharmacological blockade or siRNA-mediated inhibition of CALHM1 expression revealed that the opening of these channels provides a pathway for ATP release and the subsequent purinergic receptor-dependent activation of Cx43 hemichannels and Panx-1 channels, which further contributes to the astrocytic Ca2+ signaling. Conclusions Our findings demonstrate that activation of CALHM1 channels through NO-mediated S-nitrosylation in astrocytes in vitro is critical for the generation of glutamate-initiated astrocytic Ca2+ signaling.
dc.description.funderAgencia Nacional de Investigacin y Desarrollo
dc.fuente.origenWOS
dc.identifier.doi10.1186/s40659-024-00503-3
dc.identifier.eissn0717-6287
dc.identifier.issn0716-9760
dc.identifier.urihttps://doi.org/10.1186/s40659-024-00503-3
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/90714
dc.identifier.wosidWOS:001211501100001
dc.issue.numero1
dc.language.isoen
dc.revistaBiological research
dc.rightsacceso restringido
dc.subjectNitric oxide
dc.subjectAstrocytes
dc.subjectCa2+ signaling
dc.subjectCALHM1 channels
dc.subjectATP release
dc.subjectConnexin 43 hemichannels
dc.subjectPannexin-1 channels
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleControl of astrocytic Ca<SUP>2+</SUP> signaling by nitric oxide-dependent S-nitrosylation of Ca<SUP>2+</SUP> homeostasis modulator 1 channels
dc.typeartículo
dc.volumen57
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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