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Control of astrocytic Ca2+ signaling by nitric oxide-dependent S-nitrosylation of Ca2+ homeostasis modulator 1 channels
Puebla, Mariela; Muñoz, Manuel F.; Lillo, Mauricio A.; Contreras, Jorge E.; Figueroa, Xavier F..
Affiliation
  • Puebla, Mariela; s.af
  • Muñoz, Manuel F.; s.af
  • Lillo, Mauricio A.; s.af
  • Contreras, Jorge E.; s.af
  • Figueroa, Xavier F.; s.af
Biol. Res ; 572024.
Article in En | LILACS-Express | LILACS | ID: biblio-1564034
Responsible library: CL1.1
ABSTRACT
Background 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)-synthe-tizing 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 receptordependent 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.
Key words
Full text: 1 Collection: 01-internacional Database: LILACS Language: En Journal: Biol. Res Journal subject: BIOLOGIA Year: 2024 Document type: Article Country of publication: Chile
Full text: 1 Collection: 01-internacional Database: LILACS Language: En Journal: Biol. Res Journal subject: BIOLOGIA Year: 2024 Document type: Article Country of publication: Chile