Mechanosensory Signaling in Astrocytes

التفاصيل البيبلوغرافية
العنوان: Mechanosensory Signaling in Astrocytes
المؤلفون: Shefeeq M. Theparambil, Noemí Esteras, Philip G. Haydon, Patrick S. Hosford, Anna Hadjihambi, Anja G. Teschemacher, Alla Korsak, Mark F. Lythgoe, Egor A. Turovsky, Nephtali Marina, Alexander V. Gourine, Yichao Yu, Alice Braga
المصدر: The Journal of Neuroscience
Teschemacher, A G 2020, ' Mechanosensory signalling in astrocytes ', Journal of Neuroscience . https://doi.org/10.1523/JNEUROSCI.1249-20.2020
بيانات النشر: Society for Neuroscience, 2020.
سنة النشر: 2020
مصطلحات موضوعية: 0301 basic medicine, TRPV4, Male, Cell signaling, Baroreceptor, glia, Connexin, TRPV Cation Channels, Stimulation, Blood Pressure, Mechanotransduction, Cellular, 03 medical and health sciences, Cerebral circulation, Mice, Receptors, Purinergic P2Y1, 0302 clinical medicine, Adenosine Triphosphate, Heart Rate, mechanosensory, Physical Stimulation, Animals, Calcium Signaling, Research Articles, Mice, Knockout, Chemistry, General Neuroscience, cardiovascular, astrocytes, baroreceptor, sympathetic, Rats, 030104 developmental biology, Cerebrovascular Circulation, Connexin 43, Excitatory postsynaptic potential, Membrane channel, Female, Peptides, Neuroscience, 030217 neurology & neurosurgery, Cellular/Molecular, Brain Stem
الوصف: Mechanosensitivity is a well-known feature of astrocytes, however, its underlying mechanisms and functional significance remain unclear. There is evidence that astrocytes are acutely sensitive to decreases in cerebral perfusion pressure and may function as intracranial baroreceptors, tuned to monitor brain blood flow. This study investigated the mechanosensory signaling in brainstem astrocytes, as these cells reside alongside the cardiovascular control circuits and mediate increases in blood pressure and heart rate induced by falls in brain perfusion. It was found that mechanical stimulation-evoked Ca2+responses in astrocytes of the rat brainstem were blocked by (1) antagonists of connexin channels, connexin 43 (Cx43) blocking peptide Gap26, or Cx43 gene knock-down; (2) antagonists of TRPV4 channels; (3) antagonist of P2Y1receptors for ATP; and (4) inhibitors of phospholipase C or IP3 receptors. Proximity ligation assay demonstrated interaction between TRPV4 and Cx43 channels in astrocytes. Dye loading experiments showed that mechanical stimulation increased open probability of carboxyfluorescein-permeable membrane channels. These data suggest that mechanosensory Ca2+responses in astrocytes are mediated by interaction between TRPV4 and Cx43 channels, leading to Cx43-mediated release of ATP which propagates/amplifies Ca2+signals via P2Y1receptors and Ca2+recruitment from the intracellular stores. In astrocyte-specific Cx43 knock-out mice the magnitude of heart rate responses to acute increases in intracranial pressure was not affected by Cx43 deficiency. However, these animals displayed lower heart rates at different levels of cerebral perfusion, supporting the hypothesis of connexin hemichannel-mediated release of signaling molecules by astrocytes having an excitatory action on the CNS sympathetic control circuits.SIGNIFICANCE STATEMENTThere is evidence suggesting that astrocytes may function as intracranial baroreceptors that play an important role in the control of systemic and cerebral circulation. To function as intracranial baroreceptors, astrocytes must possess a specialized membrane mechanism that makes them exquisitely sensitive to mechanical stimuli. This study shows that opening of connexin 43 (Cx43) hemichannels leading to the release of ATP is the key central event underlying mechanosensory Ca2+responses in astrocytes. This astroglial mechanism plays an important role in the autonomic control of heart rate. These data add to the growing body of evidence suggesting that astrocytes function as versatile surveyors of the CNS metabolic milieu, tuned to detect conditions of potential metabolic threat, such as hypoxia, hypercapnia, and reduced perfusion.
وصف الملف: application/pdf
اللغة: English
تدمد: 1529-2401
0270-6474
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::048d950691e1f343934537a3549a6335
http://europepmc.org/articles/PMC7724146
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....048d950691e1f343934537a3549a6335
قاعدة البيانات: OpenAIRE